EMPA-REG Trial Protocol V4

Effectiveness research with Real World Data to support FDA’s regulatory decision making

1. RCT Details This section provides a high-level overview of the RCT that the described real-world evidence study is trying to replicate as closely as possible given the remaining limitations inherent in the healthcare databases.

1.1 Title Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME trial)

1.2 Intended aim(s) To determine the long-term cardiovascular (CV) safety of empagliflozin, as well as investigating potential benefits on macro- /microvascular outcomes.

1.3 Primary endpoint for replication and RCT finding Major Adverse Cardiovascular Events, Including CV Death, Nonfatal Myocardial Infarction (MI), and Nonfatal Stroke

1.4 Required power for primary endpoint and noninferiority margin (if applicable) For the test of noninferiority for the primary outcome with a margin of 1.3 at a one-sided level of 0.0249, at least 691 events were required to provide a power of at least 90% on the assumption of a true hazard ratio of 1.0.

1.5 Primary trial estimate targeted for replication HR = 0.86 (95% CI 0.74–0.99) comparing empagliflozin to placebo (Zinman et al., 2015)

2. Person responsible for implementation of replication in Aetion Ajinkya Pawar, Ph.D. implemented the study design in the Aetion Evidence Platform. S/he is not responsible for the validity of the design and analytic choices. All implementation steps are recorded and the implementation history is archived in the platform.

3. Data Source(s) United/Optum, MarketScan, Medicare

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4. Study Design Diagram The study design diagram visualizes key aspects of the longitudinal study design for expedited review.

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5. Cohort Identification

5.1 Cohort Summary This study will involve a new user, parallel group, cohort study design comparing empagliflozin to the DPP-4 inhibitor (DPP4i) antidiabetic class. DPP4is serve as a proxy for placebo, since this class of antidiabetic drugs is not known to have an impact on the outcome of interest. The comparison against DPP4 inhibitors is the primary comparison. The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of empagliflozin or a comparator drug (cohort entry date). Follow-up for the outcome (3P-MACE), begins the day after drug initiation. As in the trial, patients are allowed to take other antidiabetic medications during the study.

5.2 Important steps for cohort formation

5.2.1 Eligible cohort entry dates Market availability of empagliflozin in the U.S. started on August 1, 2014. • For Marketscan and Medicare: Aug 1, 2014-Dec 31, 2017 (end of data availability). • For Optum: Aug 1, 2014-Mar 31, 2019 (end of data availability).

5.2.2 Specify inclusion/exclusion criteria for cohort entry and define the index date

Inclusion and exclusion criteria were adapted from the trial as closely as possible. Definitions for all inclusion/exclusion are provided in Appendix A and are summarized in the flowcharts below.

5.3 Flowchart of the study cohort assembly

Optum Marketscan Medicare* Less Less Less Remaining Remaining Remaining Excluded Excluded Excluded Patients Patients Patients Patients Patients Patients All patients 74,864,884 191,990,035 23,466,175

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Patients who used exposure or a reference between Aug 1, 2014 to Dec -74,294,229 570,655 -191,387,941 602,094 -22,015,231 1,450,944 2017 (for Marketscan/Medicare)/March 2019 (for Optum) Patients who have continuous 6 months registration in the database -77,109 493,546 -41,856 560,238 -387,934 1,063,010 Excluded due to prior use of referent -281,236 212,310 -365,720 194,518 -738,467 324,543 Excluded due to prior use of exposure -45,709 166,601 -35,973 158,545 -25,468 299,075 Excluded because patient qualified in >1 exposure category -716 165,885 -1,192 157,353 -546 298,529 Excluded based on missing Age -6 165,879 0 157,353 0 298,529 Excluded based on missing Gender -8 165,871 0 157,353 0 298,529 Excluded based on Inclusion 1- Age >=18 -5 165,866 -44 157,309 0 298,529 Excluded based on Inclusion 2- DM Type 2 with ICD-10 codes -4,270 161,596 -6,031 151,278 -3,158 295,371 Excluded based on Inclusion 5- High risk of cardiovascular events -13,525 148,071 -15,359 135,919 -12,190 283,181 Excluded based on Inclusion 6- BMI ≤45 kg/m2 (excluded morbid obese -4,602 143,469 -3,000 132,919 -6,924 276,257 patients) Excluded based on Exclusion 2- Liver disease with ICD-10 -453 143,016 -2,028 130,891 -7,317 268,940

Excluded based on Exclusion 5- Bariatric surgery within the past two years -5 143,011 -21 130,870 -8 268,932 and other gastrointestinal surgeries that induce chronic malabsorption

Excluded based on Exclusion 6- Blood dyscrasias or any disorders causing -9,118 133,893 -5,029 125,841 -29,542 239,390 hemolysis or unstable red blood cells Excluded based on Exclusion 7- History of Malignant Neoplasm past 5 -3,550 130,343 -2,870 122,971 -11,850 227,540 years Excluded based on Exclusion 9- Obesity claim or drug 3 months prior -466 129,877 -2,810 120,161 -4,053 223,487

Excluded based on Exclusion 10- Use of corticosteroids -1504 128,373 -1147 119,014 -2,798 220,689 Excluded based on Exclusion 12- Pregnancy OR Contraceptive -398 127,975 -627 118,387 -425 220,264 Excluded based on Exclusion 13- Alcohol or drug abuse -67 127,908 -258 118,129 -568 219,696 Excluded based on Exclusion 16- Acute coronary syndrome, stroke, or -390 127,518 -677 117,452 -2,625 217,071 transient ischemic attack within 2 months Final cohort 127,518 117,452 217,071 * Medicare database includes only patients with at least one diagnosis for diabetes, heart failure, or cerebrovascular disease.

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6. Variables

6.1 Exposure-related variables:

Study drug: The study exposure of interest is initiation of empagliflozin. Initiation will be defined by no use of empagliflozin or a comparator in the prior 6 months before treatment initiation (washout period).

Comparator agents- • Initiators of empagliflozin will be compared to initiators of- o DPP4i

Because empagliflozin and comparators are frequently used as second or third line treatments of T2DM, we expect it to be unlikely that empagliflozin and comparators are initiated in patients with substantially different baseline risk for proposed outcomes.

6.2 Covariates: • Age • Sex • Combined Comorbidity Index (CCI), measured over the baseline covariate assessment period, defined as 180 days prior to and including index date

Covariates listed above represent only a small subset of covariates that will ultimately be controlled for in the design and analysis. We use the covariates above only for initial feasibility analyses to judge whether there is likely to be sufficient overlap between treatment groups to proceed with the study. Remaining covariates are defined only after the study has passed the initial feasibility analysis and the initial power assessment and are listed in Table 1 (Appendix B). These covariates are based on those used by Patorno et al. (2019).

6.3 Outcome variables and study follow-up:

6.3.1 Outcome variables

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Effectiveness outcomes of interest (definitions provided in Appendix A): • Primary outcome: 3-point major adverse cardiovascular events (MACE), i.e., non-fatal myocardial infarction, non-fatal stroke, or CV mortality • Secondary outcomes: Individual components: o Hospital admission for MI (for purposes of this individual component, fatal MI is included) o Hospital admission for stroke (for purposes of this individual component, fatal stroke is included) o All-cause mortality/CV mortality: § All-cause inpatient mortality identified using discharge status codes will be used as a proxy for “CV mortality” in commercial databases Information on CV mortality through data linkage with the National Death Index (NDI) will only become available at a later date for Medicare and will be used in secondary analyses.

Control outcomes of interest (control outcomes only serve to assess aspects of study validity but are not further interpreted): 1. Diabetes Ketoacidosis (we expect to see a positive association; Neal et al., 2017) 2. Heart failure (we expect to see a protective effect; Neal et al., 2017) Control outcome definitions

Outcome Definition Comments Control Outcomes Diabetic Ketoacidosis Inpatient ICD-9 diagnosis: 250.1x Note- The corresponding ICD-10 codes will also be used Heart Failure Inpatient ICD-9 diagnosis (primary diagnosis): Note- The corresponding ICD-10 codes 428.x, 398.91, 402.01, 402.11, 402.91, 404.01, 404.11, 404.91, 404.03, 404.13, 404.93 will also be used

6.3.2 Study follow-up Both as-treated (AT) and intention-to-treat (ITT) analyses will be conducted with treatment defined as the index drug on the day of cohort entry. Because adherence in the real world databases is expected to be much worse than in the trial, the AT analysis is the primary analysis, as it targets the relative hazard of outcomes on treatment.

For the AT analyses, the follow-up will start the day after initiation of empagliflozin and comparator and will continue until the earliest date of the following events:

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• The first occurrence of the outcome of interest, unless otherwise specified for selected outcomes, • The date of end of continuous registration in the database, • End of the study period, • Measured death event occurs, • Nursing home admission o Nursing home admissions are considered a censoring event because the data sources utilized typically provide little to no data on a patient, particularly on drug utilization, after admission. We will utilize this as an exclusion reason for cohorts for the same reason. • The date of drug discontinuation, defined as the date of the last continuous treatment episode of the index drug (empagliflozin and comparator) plus a defined grace period (i.e., 30 days after the end of the last prescription’s days’ supply in main analyses). • The date of augmentation or switching from an exposure to a comparator or any other agent in the comparator class and vice versa (e.g. switching from saxagliptin to linagliptin would be a censoring event); o A dosage change on the index treatment does not fulfill this criterion o An added treatment that is not part of the exposure or comparator group does not fulfill this criterion (e.g. if a empagliflozin user adds insulin, he or she does not get censored at the time of insulin augmentation)

For the ITT analyses, the censoring based on the augmentation/switching and treatment discontinuation will be replaced with a maximum allowed follow-up time of 365 days.

7. Initial Feasibility Analysis Aetion report name: For empagliflozin vs. DPP4i Optum-https://bwh-dope.aetion.com/projects/details/654/results/43641/result/0 Marketscan- https://bwh-dope.aetion.com/projects/details/655/results/43642/result/0 Medicare- https://bwh-dope.aetion.com/projects/details/653/results/43643/result/0

Date conducted: 10/29/2019

Complete Aetion feasibility analysis using age, sex, and CCI as the only covariates and the primary endpoint (Section 6.3.1) as the 7

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template outcome. No measures of association will be computed nor will incidence rates stratified by treatment group.

• Report patient characteristics by treatment group • Report summary parameters of the overall study population • Report median follow-up time by treatment group • Report reasons for censoring in the overall study population

8. Initial Power Assessment

Aetion report name: For empagliflozin vs. DPP4i Optum- https://bwh-dope.aetion.com/projects/details/654/results/43644/result/0 Marketscan- https://bwh-dope.aetion.com/projects/details/655/results/43645/result/0 Medicare- https://bwh-dope.aetion.com/projects/details/653/results/43646/result/0

Date conducted: 10/29/2019

In order to complete the initial power analysis, the dummy outcome of a 90-day gap in database enrollment will be used. This outcome is used to ensure that no information on the comparative risks of the outcomes of interest are available at this stage. Complete a 1:1 PS-matched comparative analysis using this outcome. PS should include only 3 covariates: age, sex, and combined comorbidity index. Power calculations are based on the formulas from Chow et al. (2008).

• Stop analyses until feasibility and power are reviewed by primary investigators, FDA, and assigned members of advisory board. Reviewed by PI: Jessica Franklin Date reviewed: 11/4/2019 Reviewed by FDA: Date reviewed: Reasons for stopping analysis (if required):

9. Balance Assessment after PS matching

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Aetion report name: Optum- https://bwh-dope.aetion.com/projects/details/654/results/45417/result/0 Marketscan- https://bwh-dope.aetion.com/projects/details/655/results/45418/result/0 Medicare- https://bwh-dope.aetion.com/projects/details/653/results/45419/result/0

Date conducted: 11/30/2019

After review of initial feasibility and power analyses, complete creation of the remaining covariates (see Table 1 below for list of covariates). Again, using the dummy outcome of a 90-day gap in database enrollment, complete a 1:1 PS-matched analysis. The PS should include the complete list of covariates (excluding laboratory values, which are missing in some patients).

• Provide plot of PS distributions stratified by treatment group.

Note- Please refer to Appendix B.

• Report covariate balance after matching.

Note- For Table 1, please refer to Appendix B.

• Report reasons for censoring by treatment group. Overall Referent Exposure Dummy Outcome 0 (0.00%) 0 (0.00%) 0 (0.00%) Death 228 (0.22%) 142 (0.27%) 86 (0.17%) Start of an additional exposure 3,474 (3.35%) 1,357 (2.62%) 2,117 (4.08%) End of index exposure 50,368 (48.55%) 26,107 (50.33%) 24,261 (46.77%) Specified date reached (Dec 16/Sep 17) 35,687 (34.40%) 17,006 (32.78%) 18,681 (36.01%) End of patient enrollment 11,469 (11.05%) 5,415 (10.44%) 6,054 (11.67%) Switch to other DPP4i (for censoring) + nursing home 2,526 (2.43%) 1,849 (3.56%) 677 (1.31%) admission

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• Report follow-up time by treatment group. Median Follow-Up Time (Days) [IQR] Patient Group Optum Marketscan Medicare Overall Patient Population 118 [58-243] 118 [58-268] 118 [58-215] Referent 118 [58-228] 118 [58-218] 118 [58-218] Exposure 118 [58-262] 118 [58-211] 118 [58-211]

• Report overall risk of the primary outcome. Optum Marketscan Medicare Risk per 1,000 patients 12.51 7.31 23.78

10. Final Power Assessment

Date conducted: 12/1/2019

• Re-calculate power in the appropriate excel table, using the revised number of matched patients from the PS-match in Section 9. All other parameters in the table should be the same as in Section 8. If the study is to be implemented in more than one database, copy and paste excel sheet to report power for each database separately and for the pooled analysis that uses data from all databases together. Power calculations are based on the formulas from Chow et al. (2008). o Pooled

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Superiority Analysis Non-inferiority Analysis Number of patients matched Number of patients matched

Reference 51,876 Reference 51,876 Exposed 51,876 Exposed 51,876 Risk per 1,000 patients 14.53 Risk per 1,000 patients 14.53 Desired HR from RCT 0.86 Assumed HR from RCT 1 Alpha (2-sided) 0.05 Alpha (2-sided) 0.05 Non-inferiority margin 1.3

Number of events expected 1507.51656 Number of events expected 1507.51656 Power Power 0.833482663 0.999136066

o Optum Superiority Analysis Non-inferiority Analysis Number of patients matched Number of patients matched

Reference 23,348 Reference 23,348 Exposed 23,348 Exposed 23,348 Risk per 1,000 patients 12.51 Risk per 1,000 patients 12.51 Desired HR from RCT 0.86 Assumed HR from RCT 1 Alpha (2-sided) 0.05 Alpha (2-sided) 0.05 Non-inferiority margin 1.3

Number of events expected 584.16696 Number of events expected 584.16696 Power Power 0.445473008 0.886984947

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o Marketscan Superiority Analysis Non-inferiority Analysis Number of patients matched Number of patients matched

Reference 16,256 Reference 16,256 Exposed 16,256 Exposed 16,256 Risk per 1,000 patients 7.31 Risk per 1,000 patients 7.31 Desired HR from RCT 0.86 Assumed HR from RCT 1 Alpha (2-sided) 0.05 Alpha (2-sided) 0.05 Non-inferiority margin 1.3

Number of events expected 237.66272 Number of events expected 237.66272 Power Power 0.213506619 0.524870241

o Medicare

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Superiority Analysis Non-inferiority Analysis Number of patients matched Number of patients matched

Reference 12,272 Reference 12,272 Exposed 12,272 Exposed 12,272 Risk per 1,000 patients 23.78 Risk per 1,000 patients 23.78 Desired HR from RCT 0.86 Assumed HR from RCT 1 Alpha (2-sided) 0.05 Alpha (2-sided) 0.05 Non-inferiority margin 1.3

Number of events expected 583.65632 Number of events expected 583.65632 Power Power 0.44515838 0.886719001

• Stop analyses until balance and final power assessment are reviewed by primary investigators, FDA, and assigned members of advisory board. Reviewers evaluate the results of the analyses described above in Sections 9 and 10, including numbers of patients, balance in patient characteristics, follow-up time, and reasons for censoring by treatment group, as well as overall rates of outcomes and study power. Reviewed by PI: Jessica Franklin Date reviewed: 12/5/19 Reviewed by FDA: David Martin Date reviewed: 12/20/2019 Reasons for stopping analysis (if required):

11. Study Confidence and Concerns

Deadline for voting on study confidence and listing concerns: 12/20/19

• If final feasibility and power analyses are reviewed and approved, proceed to the remaining protocol steps. • All study team and advisory board members that review this protocol should at this stage provide their level of confidence for the success of the RWD study in the Google Form. This form also provides space for reviewers to list any concerns that they feel may

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contribute to a failure to replicate the findings of the RCT, including differences in study populations, poor measurement of study variables, or residual confounding. All responses will be kept confidential and individual-level results will only be shared with the individual respondent.

12. Register study protocol on clinicalTrials.gov

Date conducted:

• Register the study on clinicalTrials.gov and upload this document.

13. Comparative Analyses

Aetion report name: Date conducted:

13.1 For primary analysis:

• In the PS-matched cohort from Section 9, calculate the HR for each outcome for empagliflozin versus referent patients using a Cox proportional hazards model.

13.2 For secondary analyses:

• In the pre-matched cohort, perform asymmetrical trimming to remove patients with PS values below the 2.5th percentile of treated patients and above the 97.5th percentile of untreated patients. In the trimmed cohort, calculate the HR for empagliflozin versus referent patients using a Cox proportional hazards model, adjusting for deciles of the PS.

14. Requested Results

14.1 Results from primary and secondary analyses:

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Separately for each endpoint: Analysis No. exposed events No. referent events Exposed rate Referent rate HR (95% CI)

Crude Primary analysis Analysis 2 ... HR, Hazard Ratio; CI, Confidence Interval.

15. References

American Diabetes Association. 8. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S73-S85. doi:10.2337/dc18-S008.

Chow S, Shao J, Wang H. 2008. Sample Size Calculations in Clinical Research. 2nd Ed. Chapman & Hall/CRC Biostatistics Series. page 177

Patorno E, Pawar A, Franklin JM, et al. Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study. Circulation. 2019;139:2822-30.

Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. New England Journal of Medicine. 2015;373(22):2117-28.

# Empa-Reg trial definitions Implementation in routine care References/Rationale Color coding

Please see the following Google Drive for further details or any missing information: Trial details- Secondary indication; 4a- Unintended S with label change Criteria https://drive.google.com/open?id=1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV

ICD-10 codes are not listed in this document because of excel cell size limitations and excessive number of ICD-10 codes. Full ICD-10 code lists will be available in the above Google Drive Folder (link above). ICD-9 to EXPOSURE vs. COMPARISON ICD-10 code conversions were completed using a SAS macro that implements forward/ backward mapping Adequate mapping in claims based on the CMS ICD-9 to ICD-10 mapping: https://www.nber.org/data/icd9-icd-10-cm-and-pcs-crosswalk- general-equivalence-mapping.html

Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin empagliflozin 10 mg, empagliflozin 25 mg, or placebo Empagliflozin vs. individual non-gliflozin antidiabetic class (ie, a DPP-4i, a GLP-1RA, and a sulfonylurea) antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 Intermediate mapping in claims http://dx.doi.org/10.1136/bmj.k119 PRIMARY OUTCOME Poor mapping or cannot be measured in claims

For MI: Measured 1 days after drug initiation in diagnosis position specified below and inpatient care setting: PPV 94% in Medicare claims data [Kiyota Y, Schneeweiss S, Glynn RJ, Cannuscio CC, Avorn J, Solomon DH. Inpatient mortality/MI/Stroke -- Accuracy of Medicare claims-based diagnosis of acute myocardial infarction: estimating positive predictive value on the basis of review of hospital records. American heart journal 2004;148:99-104.] For MI PPV 88.4% in commercially-insured population [Wahl PM, Rodgers K, Schneeweiss S, et al. Validation of Any diagnosis position in inpatient care setting claims-based diagnostic and procedure codes for cardiovascular and gastrointestinal serious adverse events in ICD-9 diagnosis: 410.X (acute myocardial infarction) excluding 410.x2 (subsequent episode of care) a commercially-insured population. Pharmacoepidemiology and Drug Safety 2010;19:596-603.] For stroke: For stroke PPV of 85% or higher for ischemic stroke Primary composite endpoint of time to occurrence of CV death, non-fatal MI, non-fatal stroke. HR = 0.86 (95% CI 0.74–0.99) Primary diagnosis position in inpatient care setting Can't be measured in claims but not important for the analysis PPV ranging from 80% to 98% for hemorrhagic stroke ICD-9 discharge diagnosis: [Andrade SE, Harrold LR, Tjia J, et al. A systematic review of validated methods for identifying 430.xx Subarachnoid hemorrhage (SAH) cerebrovascular accident or transient ischemic attack using administrative data. Pharmacoepidemiology and 431.xx Intracerebral hemorrhage (ICH) Drug Safety 2012;21 Suppl 1:100-28.] 433.x1 Occlusion and stenosis of precerebral arteries with cerebral infarction [Tirschwell DL, Longstreth WT, Jr. Validating administrative data in stroke research. Stroke; a journal of 434.xx (excluding 434.x0) Occlusion and stenosis of cerebral arteries with cerebral infarction cerebral circulation 2002;33:2465-70.] 436.x Acute, but ill-defined cerebrovascular events [Roumie CL, Mitchel E, Gideon PS, Varas-Lorenzo C, Castellsague J, Griffin MR. Validation of ICD-9 codes with a high positive predictive value for incident strokes resulting in hospitalization using Medicaid health Mortality- See Mortality Sheet. data. Pharmacoepidemiology and drug safety 2008;17:20-6.]

INCLUSION CRITERIA 1 Age ≥18 years (For Japan: Age ≥20 years);(For India: Age ≥18 years and ≤65 years) Age ≥18 years at drug initiation

Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 http://dx.doi.org/10.1136/bmj.k119 Measured 180 days prior to drug initiation in any diagnosis position and the inpatient or outpatient care setting 2 Diagnosis of type 2 diabetes mellitus prior to informed consent Type 2 Diabetes ICD-9 diagnosis: 250.x0, 250.x2 Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study." Circulation. 2019 Apr 8. doi: 10.1161/CIRCULATIONAHA.118.039177

3 On a diet and exercise regimen N/A 4 Insufficient glycemic control, defined as either: - Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 http://dx.doi.org/10.1136/bmj.k119 • Drug-naïve (no anti-diabetes agents for >=12 weeks prior to randomization) + HbA1c ≥7.0% (≥53 mmol/mol) and ≤9.0% (≤75 mmol/mol) at 4a (Covered below in 4b) screening Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study." Circulation. 2019 Apr 8. doi: 10.1161/CIRCULATIONAHA.118.039177 During the cohort creation, depending on the comparison group, we will require new-use (defined as no use 180 days • Taking any background anti-diabetes therapy (except pioglitazone in Japan) + HbA1c ≥7.0% (≥53 mmol/mol) and ≤10.0% (≤86 mmol/mol) prior to index date) of empagliflozin and a comparator drug at screening 4b – Background anti-diabetes therapy had to be unchanged for ≥12 weeks prior to randomization – If background anti-diabetes therapy included insulin, insulin dose had to be unchanged by >10% from the dose at randomization in the - previous 12 weeks

Measured 61 days prior to drug initiation to 3650 days prior to drug initiation in any diagnosis position and the inpatient or outpatient care setting Stable angina ICD-9 diagnosis: 413.xx

Measured 365 days prior to drug initiation as a dispensing of one of the following medications 5 High risk of cardiovascular events, defined by >=1 of the following: ACE inhibitor Benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril ARB Azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan Calcium channel blocker Diltiazem, mibefradil, verapamil, amlodipine, clevidipine, bepridil, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine Nitrates Nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, ranolazine Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 Measured 61 days prior to drug initiation to 3650 days prior to drug initiation in any diagnosis position and the inpatient http://dx.doi.org/10.1136/bmj.k119 or outpatient care setting - 5a • History of myocardial infarction >2 months prior to informed consent Acute MI ICD-9 diagnosis: 410.xx, Old MI ICD-9 diagnosis: 412.xx Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study." Circulation. 2019 Apr 8. doi: 10.1161/CIRCULATIONAHA.118.039177 • Evidence of multi-vessel CAD i.e. in ≥ 2 major coronary arteries or the left main coronary artery, documented by any of the following: -

Measured 1 days prior to drug initiation to 3650 days prior to drug initiation in any diagnosis position and the inpatient – Presence of significant stenosis: ≥50% luminal narrowing during angiography (coronary or multi-slice computed tomography) or outpatient care setting Coronary atherosclerosis and other forms of chronic ischemic heart disease ICD9 diagnosis: 414.xx

Coronary revascularization: – Previous revascularization (percutaneous transluminal coronary angioplasty ± stent or coronary artery bypass graft >2 months prior to consent CABG: Measured 61 days prior to drug initiation to 3650 days prior to drug initiation in any procedure position and inpatient care setting - CPT-4: 33510 – 33536, 33545, 33572. OR – Measured 61 days prior to drug initiation to 3650 days prior to drug initiation in any procedure position and inpatient or outpatient care setting - ICD-9 procedure: 36.1x, 36.2x

PTCA: Measured 61 days prior to drug initiation to 3650 days prior to drug initiation in any procedure position and inpatient care setting - CPT-4: 92973, 92982, 92984, 92995, 92996, 92920 – 92921, 92924 – 92925, 92937, 92938, 92941, Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin 92943, 92944 antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 OR – http://dx.doi.org/10.1136/bmj.k119 Measured 61 days prior to drug initiation to 3650 days prior to drug initiation in any procedure position and inpatient or outpatient care setting - ICD-9 procedure: 00.66, 36.01, 36.02, 36.03, 36.05, 36.09 5b Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: – The combination of revascularization in one major coronary artery and significant stenosis A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study." Circulation. Stenting: 2019 Apr 8. doi: 10.1161/CIRCULATIONAHA.118.039177 Measured 61 days prior to drug initiation to 3650 days prior to drug initiation in any procedure position and inpatient care setting- CPT-4: 92980, 92981, 92928 – 92929, 92933 - 92934 OR – Measured 61 days prior to drug initiation to 3650 days prior to drug initiation in any procedure position and inpatient or outpatient care setting- ICD-9 procedure: 36.06, 36.07

Transmyocardial revascularization: Measured 61 days prior to drug initiation to 3650 days prior to drug initiation in any procedure position and inpatient care setting- CPT-4: 33140, 33141 OR – Measured 61 days prior to drug initiation to 3650 days prior to drug initiation in any procedure position and inpatient or outpatient care setting- ICD-9 procedure: 36.31-36.34 • Evidence of single-vessel CAD, ≥50% luminal narrowing during angiography (coronary or multi-slice computed tomography) not - subsequently successfully revascularized, with at least 1 of the following: – A positive non-invasive stress test for ischemia -

Measured 365 days prior to drug initiation in any diagnosis position and the inpatient care setting – Hospital discharge for unstable angina ≤12 months prior to consent ACS/unstable angina ICD-9 diagnosis: 411.xx

Measured 61 days prior to drug initiation to 3650 days prior to drug initiation in any diagnosis position and the outpatient care setting 5c • Unstable angina >2 months prior to consent with evidence of single- or multi-vessel CAD ACS/unstable angina ICD-9 diagnosis: 411.xx

Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 Measured 61 days prior to drug initiation to 3650 days prior to drug initiation in any diagnosis position and the inpatient http://dx.doi.org/10.1136/bmj.k119 5d • History of stroke (ischemic or hemorrhagic) >2 months prior to consent or outpatient care setting Any stroke ICD-9 diagnosis: 430.xx, 431.xx, 433.xx, 434.xx, 436.xx Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study." Circulation. 2019 Apr 8. doi: 10.1161/CIRCULATIONAHA.118.039177 Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 http://dx.doi.org/10.1136/bmj.k119 Measured 180 days prior to drug initiation in any procedure position and the inpatient or outpatient care setting • Occlusive peripheral artery disease documented by any of the following: Peripheral arterial stenting or surgical revasculariztion ICD-9 procedure: 39.25, 39.50, 39.99 Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study." Circulation. 2019 Apr 8. doi: 10.1161/CIRCULATIONAHA.118.039177

Measured 180 days prior to drug initiation in any procedure position and the inpatient or outpatient care setting Lower-extremity bypass: ICD-9 procedure: 39.25, 39.29 (Outpatient only) CPT-4: 35351, 35355, 35361, 35363, 35371, 35372, 35521, 35533, 35541, 35546, 35548, 35549, 35551, 35556, 35558, 35563, 35565, 35566, 35571, 35621, 35623, 35641, 35646, 35647, 35651, 35654, 35656, Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin 35661, 35663, 35666, 35671, 35570, 35582, 35583, 35585, 35587, 35637, 35638, 35681, 35682, 35683 antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 Lower-extermity endarterectomy, stenting, angioplasty, or atherectomy: http://dx.doi.org/10.1136/bmj.k119 – Limb angioplasty, stenting, or bypass surgery ICD-9 procedure: 38.18, 38.19 (Outpatient only) CPT-4: 35454, 35456, 35459, 35470, 35473, 35474, 35482, 35483, 35485, 35492, 35493, 35495, Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: 37207, 37208, 37220-327235 A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study." Circulation. Other peripheral vascular surgery: 2019 Apr 8. doi: 10.1161/CIRCULATIONAHA.118.039177 ICD-9 procedure: 38.08, 38.09, 38.38, 38.39,38.48, 38.49, 39.5x, 39.9x (Outpatient only) CPT-4: 35256, 35286, 35381, 35879 5e

Measured 180 days prior to drug initiation in any diagnosis/procedure position and the inpatient or outpatient care Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin setting antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 Lower extremity amputation ICD-9 diagnosis: V49.7x http://dx.doi.org/10.1136/bmj.k119 – Limb or foot amputation due to circulatory insufficiency ICD-9 procedure: 84.10-84.18 (Outpatient only) CPT-4: 27590, 27591, 27592, 27880, 27881, 27882, 27884, 27886, 27888, 27889, 28800, 28805, Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: 28810, 28820, 28825 A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study." Circulation. 2019 Apr 8. doi: 10.1161/CIRCULATIONAHA.118.039177 5e

Measured 180 days prior to drug initiation in any diagnosis position and the inpatient or outpatient care setting – Ankle brachial index <0.9 in ≥1 ankle Ankle brachial index <0.9 ICD-9 diagnosis: 440.21

Measured 180 days prior to drug initiation in any diagnosis position and the inpatient or outpatient care setting 6 BMI ≤45 kg/m2 at baseline Morbid Obesity ICD-9 diagnosis: 278.01 7 An estimated glomerular filtration rate (eGFR) of at least 30 ml per minute per 1.73 m2 of body-surface area N/A 8 Signed and dated written informed consent prior to screening in accordance with Good Clinical Practice and local legislation N/A EXCLUSION CRITERIA we decided not to apply this criteria because we can captured hyperglycemia but can't capture severity of it Uncontrolled hyperglycemia with glucose >240 mg/dL (>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a 1 N/A and we may end up losing many patients at this step. In case we decide to apply it, the codes would be ICD-9 second measurement (not on the same day) 790.21 and ICD-10 R73.01

3 Planned cardiac surgery or angioplasty within 3 months N/A Estimated glomerular filtration rate <30 ml/min/1.73m2 (according to the Modification of Diet in Renal Disease equation) at screening or 4 N/A N/A during run-in phase Measured 730 days prior to drug initiation in any procedure position and inpatient or outpatient care setting CPT-4: 43644 -LRYBG -Laparoscopic Roux-en-Y gastric bypass (Roux limb 150 cm or less) 43645 -LRYGBX- Laparoscopic gastric bypass with small intestine reconstruction to Hatoum, Ida J, et al. "Clinical Factors Associated With Remission of Obesity-Related Comorbidities After 5 Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption limit absorption Bariatric Surgery." JAMA Surg. 2016;151(2):130-137. doi:10.1001/jamasurg.2015.3231 43770 -LAGB- Laparoscopic adjustable gastric band 43846 -ORYGB- Open Roux-en-Y gastric bypass (Roux limb 150 cm or less) 43847 -ORYGBX- Open gastric bypass with small intestine reconstruction to limit absorption

Measured 180 days prior to and including day of drug initiation in any diagnosis position and inpatient or outpatient care setting Diseases of the blood and blood-forming organs ICD-9 diagnosis: 280.xx-289.xx, ICD-10 diagnosis: D50.xx-D77.xx 6 Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells e.g. malaria, babesiosis, hemolytic anemia) Malignant neoplasms of lymphoid, hematopoietic and related tissue ICD-9 diagnosis: 200.xx-208.xx, ICD-10 diagnosis: C81.xx-C96.xx Hemochromatosis ICD-9 diagnosis: 275.0x, ICD-10 diagnosis: E83.11x

Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 http://dx.doi.org/10.1136/bmj.k119 Measured 1825 days prior to drug initiation in any diagnosis position and inpatient or outpatient care setting 7 Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years History of malignant neoplasm ICD-9 diagnosis: 140.xx-208.xx (except 173.xx, non-melanoma skin cancer) Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study." Circulation. 2019 Apr 8. doi: 10.1161/CIRCULATIONAHA.118.039177 8 Contraindications to background therapy according to the local label N/A

Measured 90 days prior to drug initiation as a dispensing of one of the following medications Use of orlistat, lorcaserin, phentermine/topiramate (fixed combo), bupropion/naltrexone(fixed combo), phentermine, diethylpropion, phendimetrazine, benzphetamine, sibutramine, dexfenfluramine, fenfluramine Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 OR http://dx.doi.org/10.1136/bmj.k119 Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at time of screening leading to unstable body 9 weight (e.g. surgery, aggressive diet regimen, etc.) Measured 90 days prior to drug initiation in any diagnosis/procedure position and inpatient or outpatient care setting Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: ICD-9 diagnosis: 278.0, 278.00, 278.01, 278.03, 539.xx, 649.1x, 649.2x, V85.3x, V85.4x A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study." Circulation. ICD-9 procedure: 43.82, 43.89, 44.31, 44.38, 44.39, 44.68, 44.69, 44.95, 45.51, 45.91 2019 Apr 8. doi: 10.1161/CIRCULATIONAHA.118.039177 CPT-4: 43644, 43645, 43659, 43770, 43842, 43843, 43844, 43845, 43846, 43847, 43999, S2082

Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 Measured 42 days prior to drug initiation as a dispensing of one of the following medications http://dx.doi.org/10.1136/bmj.k119 Treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed 10 Corticosteroids: Cortisone, hydrocortisone, prednisone, prednisolone, methylprednisolone, triamcinolone, consent dexamethasone, betamethasone Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study." Circulation. 2019 Apr 8. doi: 10.1161/CIRCULATIONAHA.118.039177

11 Any uncontrolled endocrine disorder except T2DM - We are unable to capture "uncontrolled" endocrine disorders. Measured 180 days prior to and including day of drug initiation in any diagnosis position and inpatient or outpatient care setting- Encounter for contraceptive management ICD-9 diagnosis: V25 OR Krumme, Alexis A, et. al. “Study protocol for the dabigatran, apixaban, rivaroxaban, edoxaban, warfarin Pregnancy - See "Pregnancy" for ICD-9 diagnosis and procedure codes. comparative effectiveness research study.” J. Comp. Eff. Res. (2018):7(1), 57–66. doi: 10.2217/cer-2017- OR 0053. Measured 180 days prior to and including day of drug initiation as a dispensing of one of the following medications Non-oral contraceptives (brand names)- We excluded patients using contraceptives because this trial includes non-pregnant women, patients without Depo-subQ childbearing potential, and patients who have childbearing potential but are taking precautions such as oral Pre-menopausal women (last menstruation ≤1 year prior to informed consent) who were nursing, pregnant, or of child-bearing potential and Provera 104 contraceptives (among many other ways) to avoid pregnancy during the trial period. It is impossible to 12 were not practicing an acceptable method of birth control, or did not plan to continue using this method throughout the study, or did not Depo-Provera, generic implement such inclusion in real-world data, as childbearing potential is not recorded in claims. In this trials agree to submit to periodic pregnancy testing during the trial Mirena setting, this limitation to implement as an inclusion criteria is due to the following: i) lack of recording of Ortho Evra contraceptives and other precautions to avoid pregnancy and ii) patients with diabetes and baseline CV tend NuvaRing to be older and are not likely to be at childbearing age. Therefore, we assumed that patients taking oral Implanon contraceptives have childbearing potential, so if they were to stop contraceptive use during follow-up, they Oral contraceptives (generic names)- See "oral contraceptives - generic" sheet. could then become pregnant. Also, just to note, this exclusion of contraceptives use excludes very few Oral contraceptives (brand names)- See "oral contraceptives - brand" sheet. patients (typically less than 0.1% of patients).

– Acceptable methods of birth control include tubal ligation, transdermal patch, intrauterine devices/systems, oral, implantable or injectable contraceptives, sexual abstinence, double barrier method, vasectomy of partner

Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin Measured 180 days prior to and including day of drug initiation in any diagnosis position and inpatient or outpatient antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 care setting- http://dx.doi.org/10.1136/bmj.k119 Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to Alcohol abuse or dependence ICD-9 diagnosis: 291.xx, 303.xx, 305.0x, 571.0x, 571.1x, 571.2x, 571.3x, 357.5x, 425.5x, 13 decreased compliance with study procedures or study drug intake E860.0x, V11.3x Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: Drug abuse or dependence ICD-9 diagnosis: 292.xx, 304.xx, 305.2x-305.9x, 648.3x A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study." Circulation. 2019 Apr 8. doi: 10.1161/CIRCULATIONAHA.118.039177 Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial or participating in another 14 N/A trial involving an investigational drug and/or follow-up Any clinical condition that would jeopardize patient safety while participating in this clinical trial (in Canada, this included current genito- 15 N/A urinal infection or genito-urinal infection within 2 weeks prior to informed consent)

Measured 60 days prior to day of drug initiation in any diagnosis position and inpatient or outpatient care setting- ACS/unstable angina ICD-9 diagnosis: 411.xx Stroke ICD-9 diagnosis : Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin 430.xx Subarachnoid hemorrhage (SAH) antidiabetic drugs: population based cohort study." BMJ 2018;360:k119 431.xx Intracerebral hemorrhage (ICH) http://dx.doi.org/10.1136/bmj.k119 16 Acute coronary syndrome, stroke, or transient ischemic attack within 2 months prior to informed consent 433.x1 Occlusion and stenosis of precerebral arteries with cerebral infarction 434.x1 Occlusion and stenosis of cerebral arteries with cerebral infarction Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: 436.x Acute, but ill-defined cerebrovascular events. A First Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study." Circulation. TIA ICD-9 diagnosis: 435.xx 2019 Apr 8. doi: 10.1161/CIRCULATIONAHA.118.039177 Acute MI ICD-9 diagnosis: 410.X (acute myocardial infarction) excluding 410.x2 (subsequent episode of care)

17 In South Africa: blood pressure >160/100 mmHg at screening N/A Trial ID sNDA21 Trial Name (with web links) EMPA-REG OUTCOME Trial Name (with pdf links) EMPA-REG OUTCOME NCT NCT01131676 Trial category Secondary indication Therapeutic Area Endocrinology RCT Category 4a- Unintended S with label change Brand Name Synjardy Generic Name Empagliflozin; metformin hydrochloride Sponsor Boehringer Ingelheim Year 2016 Measurable endpoint Primary composite endpoint of CV death, non-fatal MI, non-fatal stroke Exposure Empagliflozin Comparator Placebo Population 95% on Anti-hypertensive therapy, 80% on Lipid-lowering therapy & 89% on Anti-coagulants Trial finding HR = 0.86 (95% CI 0.74–0.99) No. of Patients 7,064 Non-inferiority margin HR = 1.3 Assay Sens. Endpoint Assay Sens. Finding 0.90. For the test of noninferiority for the primary outcome with a margin of 1.3 at a one-sided level of 0.0249, at least 691 events were Power required to provide a power of at least 90% on the assumption of a true hazard ratio of 1.0. Blinding Double-blinded Accidental superiority, the non-inferiority margin was chosen as 1.3 based on Food and Drug Administration (FDA) Guidance for Industry – Statistical Method Diabetes Mellitus – Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes Approval indication Proposes a new indication for Synjardy based on results of the cardiovascular safety study 1245.25, the EMPA-REG OUTCOME trial. Mortality- Dependent on data source.

1. All-cause mortality / inpatient mortality Identified using the vital status file-

Medicare Identified using the discharge status codes-

Optum- • 20 = EXPIRED • 21 = EXPIRED TO BE DEFINED AT STATE LEVEL • 22 = EXPIRED TO BE DEFINED AT STATE LEVEL • 23 = EXPIRED TO BE DEFINED AT STATE LEVEL • 24 = EXPIRED TO BE DEFINED AT STATE LEVEL • 25 = EXPIRED TO BE DEFINED AT STATE LEVEL • 26 = EXPIRED TO BE DEFINED AT STATE LEVEL • 27 = EXPIRED TO BE DEFINED AT STATE LEVEL • 28 = EXPIRED TO BE DEFINED AT STATE LEVEL • 29 = EXPIRED TO BE DEFINED AT STATE LEVEL • 40 = EXPIRED AT HOME (HOSPICE) • 41 = EXPIRED IN A MEDICAL FACILITY (HOSPICE) • 42 = EXPIRED - PLACE UNKNOWN (HOSPICE)

Truven- • 20 - Died • 22 - Died • 23 - Died • 24 - Died • 25 - Died • 26 - Died • 27 - Died • 28 - Died • 29 - Died • 40 - Other died status or Expired at home (Hospice claims only) (depends on year) • 41 - Other died status or Expired in medical facility (Hospice claims only) (depends on year) • 42 - Other died status or Expired - place unknown (Hospice claims only) (depends on year) • 21 - Died or Disch./Transf. to court/law enforcement (depends on year)

Medicare Identified using the discharge status codes-

2. CV mortality Information on CV mortality through data linkage with the National Death Index (NDI) will be available for Medicare at a later date. We will conduct secondary analyses using CV mortality at that time. Antidiabetic class Specific agent Notes Canagliflozin Approved 3/29/2013 Dapagliflozin SGLT2-inhibitors Empagliflozin Ertugliflozin Approved Dec 21, 2017 Glimepiride 2nd generation sulfonylureas Glipizide Glyburide Alogliptin Linagliptin DPP-4 inhibitors Saxagliptin Sitagliptin Exenatide Liraglutide

Approved April 15, 2014 and Albiglutide GLP-1 receptor agonist (GLP1-RA) discontinued July 26, 2017 Dulaglutide Approved Sep 18, 2014 Lixisenatide Approved July 28, 2016 Semaglutide Approved Dec 5, 2017 Insulin Aspart Insulin Aspart/Insulin Aspart Protamine Insulin Degludec Insulin Detemir Insulin Glargine Insulin Glulisine Insulin Insulin human isophane (NPH) Insulin human regular (search with NPH, don't want bf-pk) Insulin human regular/ Insulin human isophane (NPH) Insulin Lispro Insulin Lispro/Insulin Lispro Protamine Pioglitazone Glitazones Glitazones Rosiglitazone Nateglinide Meglitinides Repaglinide Acarbose Alpha-glucosidase inhibitors Miglitol Pramlintide Pramlintide Acetohexamide Chlorpropamide 1st generation sulfonylureas Tolazamide Tolbutamide drug_class Brand Name oral contraceptive Apri; oral contraceptive Desogen; oral contraceptive Ortho-Cept; oral contraceptive Reclipsen oral contraceptive Kariva; oral contraceptive Mircette oral contraceptive Cyclessa; oral contraceptive Velivet oral contraceptive Yasmin oral contraceptive Yaz oral contraceptive Demulen 1/35; oral contraceptive Kelnor; oral contraceptive Zovia 1/25 oral contraceptive Demulen 1/50; oral contraceptive Zovia 1/50 oral contraceptive Alesse; oral contraceptive Aviane; oral contraceptive Lessina; oral contraceptive Lutera oral contraceptive Nordette; oral contraceptive Portia; oral contraceptive Levora oral contraceptive Lybrel oral contraceptive Seasonale; oral contraceptive Quasense; oral contraceptive Jolessa oral contraceptive Seasonique oral contraceptive Empresse; oral contraceptive Triphasil; oral contraceptive Trivora oral contraceptive Ovcon 35 oral contraceptive Balziva; oral contraceptive Femcon Fe oral contraceptive Brevicon; oral contraceptive Nortrel 0.5/35; oral contraceptive Modicon; oral contraceptive Necon 0.5/35 oral contraceptive Norinyl 1/35; oral contraceptive Nortrel 1/35; oral contraceptive Ortho-Novum 1/35; oral contraceptive Necon 1/35 oral contraceptive Ovcon 50; oral contraceptive Necon 1/50 oral contraceptive Ortho-Novum 10/11 oral contraceptive Aranelle; oral contraceptive Tri-Norinyl oral contraceptive Ortho-Novum 7/7/7; oral contraceptive Necon oral contraceptive Micronor; oral contraceptive Nor-QD; oral contraceptive Camila; oral contraceptive Errin; oral contraceptive Jolivette oral contraceptive Junel 21 1/20; oral contraceptive Junel 21 Fe 1/20; oral contraceptive Loestrin 21 1/20; oral contraceptive Loestrin 21 Fe 1/20; oral contraceptive Loestrin 24 Fe; oral contraceptive Microgestin 1/20 oral contraceptive Microgestin Fe 1/20 oral contraceptive Junel 21 1.5/30; oral contraceptive Junel 21 Fe 1.5/30; oral contraceptive Loestrin 1.5/30; oral contraceptive Loestrin Fe 1.5/30 oral contraceptive Microgestin 1.5/30 oral contraceptive Microgestin Fe 1.5/30 oral contraceptive Estrostep Fe; oral contraceptive Tilia Fe; oral contraceptive TriLegest Fe oral contraceptive Ortho-Cyclen; oral contraceptive Sprintec; oral contraceptive MonoNessa; oral contraceptive Previfem oral contraceptive Ortho Tri-Cyclen Lo; oral contraceptive Tri-Previfem; oral contraceptive TriNessa oral contraceptive Ortho Tri-Cyclen; oral contraceptive Tri-Sprintec oral contraceptive Cryselle; oral contraceptive Lo/Ovral; oral contraceptive Low-Ogestrel oral contraceptive Ovral; oral contraceptive Ogestrel oral contraceptive Zovia 1/50 oral contraceptive Alesse; oral contraceptive Aviane; oral contraceptive Lessina; oral contraceptive Lutera oral contraceptive Nordette; oral contraceptive Portia; oral contraceptive Levora oral contraceptive Lybrel oral contraceptive Seasonale; oral contraceptive Quasense; oral contraceptive Jolessa oral contraceptive Seasonique oral contraceptive Empresse; oral contraceptive Triphasil; oral contraceptive Trivora oral contraceptive Ovcon 35 oral contraceptive Balziva; oral contraceptive Femcon Fe oral contraceptive Brevicon; oral contraceptive Nortrel 0.5/35; oral contraceptive Modicon; oral contraceptive Necon 0.5/35 oral contraceptive Norinyl 1/35; oral contraceptive Nortrel 1/35; oral contraceptive Ortho-Novum 1/35; oral contraceptive Necon 1/35 oral contraceptive Ovcon 50; oral contraceptive Necon 1/50 oral contraceptive Ortho-Novum 10/11 oral contraceptive Aranelle; oral contraceptive Tri-Norinyl oral contraceptive Ortho-Novum 7/7/7; oral contraceptive Necon oral contraceptive Micronor; oral contraceptive Nor-QD; oral contraceptive Camila; oral contraceptive Errin; oral contraceptive Jolivette oral contraceptive Junel 21 1/20; oral contraceptive Junel 21 Fe 1/20; oral contraceptive Loestrin 21 1/20; oral contraceptive Loestrin 21 Fe 1/20; oral contraceptive Loestrin 24 Fe; oral contraceptive Microgestin 1/20 oral contraceptive Microgestin Fe 1/20 oral contraceptive Junel 21 1.5/30; oral contraceptive Junel 21 Fe 1.5/30; oral contraceptive Loestrin 1.5/30; oral contraceptive Loestrin Fe 1.5/30 oral contraceptive Microgestin 1.5/30 oral contraceptive Microgestin Fe 1.5/30 oral contraceptive Estrostep Fe; oral contraceptive Tilia Fe; oral contraceptive TriLegest Fe oral contraceptive Ortho-Cyclen; oral contraceptive Sprintec; oral contraceptive MonoNessa; oral contraceptive Previfem oral contraceptive Ortho Tri-Cyclen Lo; oral contraceptive Tri-Previfem; oral contraceptive TriNessa oral contraceptive Ortho Tri-Cyclen; oral contraceptive Tri-Sprintec oral contraceptive Cryselle; oral contraceptive Lo/Ovral; oral contraceptive Low-Ogestrel oral contraceptive Ovral; oral contraceptive Ogestrel drug_class generic generic_ndc oral contraceptive estradiol desogestrel-ethinyl estradiol oral contraceptive estradiol desogestrel-ethinyl estradiol/ethinyl estradiol oral contraceptive estradiol drospirenone/estradiol oral contraceptive estradiol drospirenone/ethinyl estradiol/levomefolate calcium oral contraceptive estradiol estradiol oral contraceptive estradiol estradiol acetate oral contraceptive estradiol estradiol benzoate oral contraceptive estradiol estradiol cypionate oral contraceptive estradiol estradiol cypionate/medroxyprogesterone acet oral contraceptive estradiol estradiol hemihydrate, micronized oral contraceptive estradiol estradiol micronized oral contraceptive estradiol estradiol valerate oral contraceptive estradiol estradiol valerate/dienogest oral contraceptive estradiol estradiol valerate/sesame oil oral contraceptive estradiol estradiol/estrone oral contraceptive estradiol estradiol/estrone/vit b12 oral contraceptive estradiol estradiol/levonorgestrel oral contraceptive estradiol estradiol/norethindrone acetate oral contraceptive estradiol estradiol/norgestimate oral contraceptive estradiol estradiol/progesterone oral contraceptive estradiol ethinyl estradiol oral contraceptive estradiol ethinyl estradiol/drospirenone oral contraceptive estradiol ethinyl estradiol/norethindrone acetate oral contraceptive estradiol ethynodiol d-ethinyl estradiol oral contraceptive estradiol ethynodiol diacetate-ethinyl estradiol oral contraceptive estradiol etonogestrel/ethinyl estradiol oral contraceptive estradiol levonorgestrel-ethinyl estradiol oral contraceptive estradiol levonorgestrel/ethinyl estradiol and ethinyl estradiol oral contraceptive estradiol me-testosterone/eth estradiol oral contraceptive estradiol metttrn/estradiol/multivits oral contraceptive estradiol norelgestromin/ethinyl estradiol oral contraceptive estradiol norethindrone a-e estradiol oral contraceptive estradiol norethindrone a-e estradiol/fe oral contraceptive estradiol norethindrone a-e estradiol/ferrous fumarate oral contraceptive estradiol norethindrone acetate-ethinyl estradiol oral contraceptive estradiol norethindrone acetate-ethinyl estradiol/ferrous fumarate oral contraceptive estradiol norethindrone-ethin estradiol oral contraceptive estradiol norethindrone-ethinyl estradiol oral contraceptive estradiol norethindrone-ethinyl estradiol/ferrous fumarate oral contraceptive estradiol norgestimate-ethinyl estradiol oral contraceptive estradiol norgestrel-ethinyl estradiol oral contraceptive estradiol testosterone cypionate/estradiol cypionate oral contraceptive estradiol testosterone enanthate/estradiol valerate oral contraceptive estradiol testosterone/estradiol oral contraceptive levonorgestrel estradiol/levonorgestrel oral contraceptive levonorgestrel levonorgestrel oral contraceptive levonorgestrel levonorgestrel-eth estra oral contraceptive levonorgestrel levonorgestrel-eth estra/pregnancy test kit oral contraceptive levonorgestrel levonorgestrel-ethinyl estradiol oral contraceptive levonorgestrel levonorgestrel/ethinyl estradiol and ethinyl estradiol oral contraceptive norethindrone estradiol/norethindrone acetate oral contraceptive norethindrone ethinyl estradiol/norethindrone acetate oral contraceptive norethindrone leuprolide acetate/norethindrone acetate oral contraceptive norethindrone norethindrone oral contraceptive norethindrone norethindrone a-e estradiol oral contraceptive norethindrone norethindrone a-e estradiol/fe oral contraceptive norethindrone norethindrone a-e estradiol/ferrous fumarate oral contraceptive norethindrone norethindrone acetate oral contraceptive norethindrone norethindrone acetate-ethinyl estradiol oral contraceptive norethindrone norethindrone acetate-ethinyl estradiol/ferrous fumarate oral contraceptive norethindrone norethindrone-ethin estradiol oral contraceptive norethindrone norethindrone-ethinyl estrad oral contraceptive norethindrone norethindrone-ethinyl estradiol oral contraceptive norethindrone norethindrone-ethinyl estradiol/ferrous fumarate oral contraceptive norethindrone norethindrone-mestranol oral contraceptive norgestrel norgestrel oral contraceptive norgestrel norgestrel-ethinyl estradiol oral contraceptive polyestradiol phosphate polyestradiol phosphate Pregnancy Dx codes 650 NORMAL DELIVERY 660 OBSTRUCTED LABOR 661 ABNORMALITY OF FORCES OF LABOR 662 LONG LABOR 663 UMBILICAL CORD COMPLICATIONS DURING LABOR AND DELIVERY 664 TRAUMA TO PERINEUM AND VULVA DURING DELIVERY 665 OTHER OBSTETRICAL TRAUMA 667 RETAINED PLACENTA OR MEMBRANES WITHOUT HEMORRHAGE 668 COMPLICATIONS OF THE ADMINISTRATION OF ANESTHETIC OR OTHER SEDATION IN LABOR AND DELIVERY 669.94 UNSPECIFIED COMPLICATION OF LABOR AND DELIVERY POSTPARTUM CONDITION OR COMPLICATION V24 POSTPARTUM CARE AND EXAMINATION V24.0 POSTPARTUM CARE AND EXAMINATION IMMEDIATELY AFTER DELIVERY V24.1 POSTPARTUM CARE AND EXAMINATION OF LACTATING MOTHER V24.2 ROUTINE POSTPARTUM FOLLOW V27 OUTCOME OF DELIVERY V27.0 MOTHER WITH SINGLE LIVEBORN V27.1 MOTHER WITH SINGLE STILLBORN V27.2 MOTHER WITH TWINS BOTH LIVEBORN V27.3 MOTHER WITH TWINS ONE LIVEBORN AND ONE STILLBORN V27.4 MOTHER WITH TWINS BOTH STILLBORN V27.5 MOTHER WITH OTHER MULTIPLE BIRTH ALL LIVEBORN V27.6 MOTHER WITH OTHER MULTIPLE BIRTH SOME LIVEBORN V27.7 MOTHER WITH OTHER MULTIPLE BIRTH ALL STILLBORN V27.9 MOTHER WITH UNSPECIFIED OUTCOME OF DELIVERY Procedure codes 72.0 LOW FORCEPS OPERATION 72.1 LOW FORCEPS OPERATION WITH EPISIOTOMY 72.2 MID FORCEPS OPERATION 72.21 MID FORCEPS OPERATION WITH EPISIOTOMY 72.29 OTHER MID FORCEPS OPERATION 72.3 HIGH FORCEPS OPERATION 72.31 HIGH FORCEPS OPERATION WITH EPISIOTOMY 72.39 OTHER HIGH FORCEPS OPERATION 72.4 FORCEPS ROTATION OF FETAL HEAD 72.5 BREECH EXTRACTION 72.51 PARTIAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD 72.52 OTHER PARTIAL BREECH EXTRACTION 72.53 TOTAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD 72.54 OTHER TOTAL BREECH EXTRACTION 72.6 FORCEPS APPLICATION TO AFTERCOMING HEAD 72.7 VACUUM EXTRACTION 72.71 VACUUM EXTRACTION WITH EPISIOTOMY 72.79 OTHER VACUUM EXTRACTION 72.8 OTHER SPECIFIED INSTRUMENTAL DELIVERY 72.9 UNSPECIFIED INSTRUMENTAL DELIVERY 73.0 ARTIFICIAL RUPTURE OF MEMBRANES 73.01 INDUCTION OF LABOR BY ARTIFICIAL RUPTURE OF MEMBRANES 73.09 OTHER ARTIFICIAL RUPTURE OF MEMBRANES 73.1 OTHER SURGICAL INDUCTION OF LABOR 73.2 INTERNAL AND COMBINED VERSION AND EXTRACTION 73.21 INTERNAL AND COMBINED VERSION WITHOUT EXTRACTION 73.22 INTERNAL AND COMBINED VERSION WITH EXTRACTION 73.3 FAILED FORCEPS 73.4 MEDICAL INDUCTION OF LABOR 73.5 MANUALLY ASSISTED DELIVERY 73.51 MANUAL ROTATION OF FETAL HEAD 73.59 OTHER MANUALLY ASSISTED DELIVERY 73.6 EPISIOTOMY 73.8 OPERATIONS ON FETUS TO FACILITATE DELIVERY 73.9 OTHER OPERATIONS ASSISTING DELIVERY 73.91 EXTERNAL VERSION ASSISTING DELIVERY 73.92 REPLACEMENT OF PROLAPSED UMBILICAL CORD 73.93 INCISION OF CERVIX TO ASSIST DELIVERY 73.94 PUBIOTOMY TO ASSIST DELIVERY 73.99 OTHER OPERATIONS ASSISTING DELIVERY 74.0 CLASSICAL CESAREAN SECTION 74.1 LOW CERVICAL CESAREAN SECTION 74.2 EXTRAPERITONEAL CESAREAN SECTION 74.3 REMOVAL OF EXTRATUBAL ECTOPIC PREGNANCY 74.4 CESAREAN SECTION OF OTHER SPECIFIED TYPE 74.9 CESAREAN SECTION OF UNSPECIFIED TYPE 74.91 HYSTEROTOMY TO TERMINATE PREGNANCY 74.99 OTHER CESAREAN SECTION OF UNSPECIFIED TYPE 75.4 MANUAL REMOVAL OF RETAINED PLACENTA 75.5 REPAIR OF CURRENT OBSTETRIC LACERATION OF UTERUS 75.6 REPAIR OF OTHER CURRENT OBSTETRIC LACERATION 75.7 MANUAL EXPLORATION OF UTERINE CAVITY, POSTPARTUM 75.9 OTHER OBSTETRIC OPERATIONS Dx codes 650 NORMAL DELIVERY 660 OBSTRUCTED LABOR 661 ABNORMALITY OF FORCES OF LABOR 662 LONG LABOR 663 UMBILICAL CORD COMPLICATIONS DURING LABOR AND DELIVERY 664 TRAUMA TO PERINEUM AND VULVA DURING DELIVERY 665 OTHER OBSTETRICAL TRAUMA 667 RETAINED PLACENTA OR MEMBRANES WITHOUT HEMORRHAGE 668 COMPLICATIONS OF THE ADMINISTRATION OF ANESTHETIC OR OTHER SEDATION IN LABOR AND DELIVERY 669.94 UNSPECIFIED COMPLICATION OF LABOR AND DELIVERY POSTPARTUM CONDITION OR COMPLICATION V24 POSTPARTUM CARE AND EXAMINATION V24.0 POSTPARTUM CARE AND EXAMINATION IMMEDIATELY AFTER DELIVERY V24.1 POSTPARTUM CARE AND EXAMINATION OF LACTATING MOTHER V24.2 ROUTINE POSTPARTUM FOLLOW V27 OUTCOME OF DELIVERY V27.0 MOTHER WITH SINGLE LIVEBORN V27.1 MOTHER WITH SINGLE STILLBORN V27.2 MOTHER WITH TWINS BOTH LIVEBORN V27.3 MOTHER WITH TWINS ONE LIVEBORN AND ONE STILLBORN V27.4 MOTHER WITH TWINS BOTH STILLBORN V27.5 MOTHER WITH OTHER MULTIPLE BIRTH ALL LIVEBORN V27.6 MOTHER WITH OTHER MULTIPLE BIRTH SOME LIVEBORN V27.7 MOTHER WITH OTHER MULTIPLE BIRTH ALL STILLBORN V27.9 MOTHER WITH UNSPECIFIED OUTCOME OF DELIVERY Procedure codes 72.0 LOW FORCEPS OPERATION 72.1 LOW FORCEPS OPERATION WITH EPISIOTOMY 72.2 MID FORCEPS OPERATION 72.21 MID FORCEPS OPERATION WITH EPISIOTOMY 72.29 OTHER MID FORCEPS OPERATION 72.3 HIGH FORCEPS OPERATION 72.31 HIGH FORCEPS OPERATION WITH EPISIOTOMY 72.39 OTHER HIGH FORCEPS OPERATION 72.4 FORCEPS ROTATION OF FETAL HEAD 72.5 BREECH EXTRACTION 72.51 PARTIAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD 72.52 OTHER PARTIAL BREECH EXTRACTION 72.53 TOTAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD 72.54 OTHER TOTAL BREECH EXTRACTION 72.6 FORCEPS APPLICATION TO AFTERCOMING HEAD 72.7 VACUUM EXTRACTION 72.71 VACUUM EXTRACTION WITH EPISIOTOMY 72.79 OTHER VACUUM EXTRACTION 72.8 OTHER SPECIFIED INSTRUMENTAL DELIVERY 72.9 UNSPECIFIED INSTRUMENTAL DELIVERY 73.0 ARTIFICIAL RUPTURE OF MEMBRANES 73.01 INDUCTION OF LABOR BY ARTIFICIAL RUPTURE OF MEMBRANES 73.09 OTHER ARTIFICIAL RUPTURE OF MEMBRANES 73.1 OTHER SURGICAL INDUCTION OF LABOR 73.2 INTERNAL AND COMBINED VERSION AND EXTRACTION 73.21 INTERNAL AND COMBINED VERSION WITHOUT EXTRACTION 73.22 INTERNAL AND COMBINED VERSION WITH EXTRACTION 73.3 FAILED FORCEPS 73.4 MEDICAL INDUCTION OF LABOR 73.5 MANUALLY ASSISTED DELIVERY 73.51 MANUAL ROTATION OF FETAL HEAD 73.59 OTHER MANUALLY ASSISTED DELIVERY 73.6 EPISIOTOMY 73.8 OPERATIONS ON FETUS TO FACILITATE DELIVERY 73.9 OTHER OPERATIONS ASSISTING DELIVERY 73.91 EXTERNAL VERSION ASSISTING DELIVERY 73.92 REPLACEMENT OF PROLAPSED UMBILICAL CORD 73.93 INCISION OF CERVIX TO ASSIST DELIVERY 73.94 PUBIOTOMY TO ASSIST DELIVERY 73.99 OTHER OPERATIONS ASSISTING DELIVERY 74.0 CLASSICAL CESAREAN SECTION 74.1 LOW CERVICAL CESAREAN SECTION 74.2 EXTRAPERITONEAL CESAREAN SECTION 74.3 REMOVAL OF EXTRATUBAL ECTOPIC PREGNANCY 74.4 CESAREAN SECTION OF OTHER SPECIFIED TYPE 74.9 CESAREAN SECTION OF UNSPECIFIED TYPE 74.91 HYSTEROTOMY TO TERMINATE PREGNANCY 74.99 OTHER CESAREAN SECTION OF UNSPECIFIED TYPE 75.4 MANUAL REMOVAL OF RETAINED PLACENTA 75.5 REPAIR OF CURRENT OBSTETRIC LACERATION OF UTERUS 75.6 REPAIR OF OTHER CURRENT OBSTETRIC LACERATION 75.7 MANUAL EXPLORATION OF UTERINE CAVITY, POSTPARTUM 75.9 OTHER OBSTETRIC OPERATIONS Dx codes 650 NORMAL DELIVERY 660 OBSTRUCTED LABOR 661 ABNORMALITY OF FORCES OF LABOR 662 LONG LABOR 663 UMBILICAL CORD COMPLICATIONS DURING LABOR AND DELIVERY 664 TRAUMA TO PERINEUM AND VULVA DURING DELIVERY 665 OTHER OBSTETRICAL TRAUMA 667 RETAINED PLACENTA OR MEMBRANES WITHOUT HEMORRHAGE 668 COMPLICATIONS OF THE ADMINISTRATION OF ANESTHETIC OR OTHER SEDATION IN LABOR AND DELIVERY 669.94 UNSPECIFIED COMPLICATION OF LABOR AND DELIVERY POSTPARTUM CONDITION OR COMPLICATION V24 POSTPARTUM CARE AND EXAMINATION V24.0 POSTPARTUM CARE AND EXAMINATION IMMEDIATELY AFTER DELIVERY V24.1 POSTPARTUM CARE AND EXAMINATION OF LACTATING MOTHER V24.2 ROUTINE POSTPARTUM FOLLOW V27 OUTCOME OF DELIVERY V27.0 MOTHER WITH SINGLE LIVEBORN V27.1 MOTHER WITH SINGLE STILLBORN V27.2 MOTHER WITH TWINS BOTH LIVEBORN V27.3 MOTHER WITH TWINS ONE LIVEBORN AND ONE STILLBORN V27.4 MOTHER WITH TWINS BOTH STILLBORN V27.5 MOTHER WITH OTHER MULTIPLE BIRTH ALL LIVEBORN V27.6 MOTHER WITH OTHER MULTIPLE BIRTH SOME LIVEBORN V27.7 MOTHER WITH OTHER MULTIPLE BIRTH ALL STILLBORN V27.9 MOTHER WITH UNSPECIFIED OUTCOME OF DELIVERY Procedure codes 72.0 LOW FORCEPS OPERATION 72.1 LOW FORCEPS OPERATION WITH EPISIOTOMY 72.2 MID FORCEPS OPERATION 72.21 MID FORCEPS OPERATION WITH EPISIOTOMY 72.29 OTHER MID FORCEPS OPERATION 72.3 HIGH FORCEPS OPERATION 72.31 HIGH FORCEPS OPERATION WITH EPISIOTOMY 72.39 OTHER HIGH FORCEPS OPERATION 72.4 FORCEPS ROTATION OF FETAL HEAD 72.5 BREECH EXTRACTION 72.51 PARTIAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD 72.52 OTHER PARTIAL BREECH EXTRACTION 72.53 TOTAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD 72.54 OTHER TOTAL BREECH EXTRACTION 72.6 FORCEPS APPLICATION TO AFTERCOMING HEAD 72.7 VACUUM EXTRACTION 72.71 VACUUM EXTRACTION WITH EPISIOTOMY 72.79 OTHER VACUUM EXTRACTION 72.8 OTHER SPECIFIED INSTRUMENTAL DELIVERY 72.9 UNSPECIFIED INSTRUMENTAL DELIVERY 73.0 ARTIFICIAL RUPTURE OF MEMBRANES 73.01 INDUCTION OF LABOR BY ARTIFICIAL RUPTURE OF MEMBRANES 73.09 OTHER ARTIFICIAL RUPTURE OF MEMBRANES 73.1 OTHER SURGICAL INDUCTION OF LABOR 73.2 INTERNAL AND COMBINED VERSION AND EXTRACTION 73.21 INTERNAL AND COMBINED VERSION WITHOUT EXTRACTION 73.22 INTERNAL AND COMBINED VERSION WITH EXTRACTION 73.3 FAILED FORCEPS 73.4 MEDICAL INDUCTION OF LABOR 73.5 MANUALLY ASSISTED DELIVERY 73.51 MANUAL ROTATION OF FETAL HEAD 73.59 OTHER MANUALLY ASSISTED DELIVERY 73.6 EPISIOTOMY 73.8 OPERATIONS ON FETUS TO FACILITATE DELIVERY 73.9 OTHER OPERATIONS ASSISTING DELIVERY 73.91 EXTERNAL VERSION ASSISTING DELIVERY 73.92 REPLACEMENT OF PROLAPSED UMBILICAL CORD 73.93 INCISION OF CERVIX TO ASSIST DELIVERY 73.94 PUBIOTOMY TO ASSIST DELIVERY 73.99 OTHER OPERATIONS ASSISTING DELIVERY 74.0 CLASSICAL CESAREAN SECTION 74.1 LOW CERVICAL CESAREAN SECTION 74.2 EXTRAPERITONEAL CESAREAN SECTION 74.3 REMOVAL OF EXTRATUBAL ECTOPIC PREGNANCY 74.4 CESAREAN SECTION OF OTHER SPECIFIED TYPE 74.9 CESAREAN SECTION OF UNSPECIFIED TYPE 74.91 HYSTEROTOMY TO TERMINATE PREGNANCY 74.99 OTHER CESAREAN SECTION OF UNSPECIFIED TYPE 75.4 MANUAL REMOVAL OF RETAINED PLACENTA 75.5 REPAIR OF CURRENT OBSTETRIC LACERATION OF UTERUS 75.6 REPAIR OF OTHER CURRENT OBSTETRIC LACERATION 75.7 MANUAL EXPLORATION OF UTERINE CAVITY, POSTPARTUM 75.9 OTHER OBSTETRIC OPERATIONS Optum MarketScan Medicare

BEFORE PS MATCHING

The c-statistics for the propensity score model, pre-matching was 0.809. The post-matching c-statistic The c-statistics for the propensity score model, pre-matching was 0.821. The post-matching The c-statistics for the propensity score model, pre-matching was 0.851. The post-matching c-statistic was 0.524. c-statistic was 0.537. was 0.528.

AFTER PS MATCHING Unmatched

Optum MarketScan Medicare POOLED Exposure - Empagliflozin Exposure - Empagliflozin Exposure - Exposure - Empagliflozin Variable Reference- DPP4i v2 v3 Reference- DPP4i v2 v3 Reference- DPP4i v2 Empagliflozin v3 Reference- DPP4i v2 v3 St. Diff. Number of patients 99,903 27,394 98,345 18,912 203,294 13,156 401,542 59,462 Age ...mean (sd) 64.93 (11.69) 60.53 (10.62) 58.66 (11.12) 55.47 (8.77) 74.08 (6.94) 71.46 (5.19) 68.03 (9.42) 61.34 (9.08) 0.72 ...median [IQR] 66.00 [57.00, 73.00] 61.00 [53.00, 68.00] 58.00 [52.00, 64.00] 56.00 [50.00, 61.00] 73.00 [68.00, 78.00]70.00 [68.00, 74.00] 67.58 (9.42) 61.40 (9.08) 0.67 Age categories without zero category ...18 - 54; n (%) 19,490 (19.5%) 7,748 (28.3%) 33,966 (34.5%) 7,944 (42.0%) 0 (0.0%) 0 (0.0%) 53,456 (13.3%) 15,692 (26.4%) -0.33 ...55 - 64; n (%) 23,551 (23.6%) 8,844 (32.3%) 41,612 (42.3%) 9,123 (48.2%) 1,132 (0.6%) 43 (0.3%) 66,295 (16.5%) 18,010 (30.3%) -0.33 ...65 - 74; n (%) 36,281 (36.3%) 8,539 (31.2%) 13,769 (14.0%) 1,483 (7.8%) 119,235 (58.7%) 9,986 (75.9%) 169,285 (42.2%) 20,008 (33.6%) 0.18 ...>= 75; n (%) 20,581 (20.6%) 2,263 (8.3%) 8,998 (9.1%) 362 (1.9%) 82,927 (40.8%) 3,127 (23.8%) 112,506 (28.0%) 5,752 (9.7%) 0.48 Gender without zero category- United ...Males; n (%) 53,340 (53.4%) 16,618 (60.7%) 57,603 (58.6%) 11,785 (62.3%) 92,595 (45.5%) 7,494 (57.0%) 203,538 (50.7%) 35,897 (60.4%) -0.20 ...Females; n (%) 46,563 (46.6%) 10,776 (39.3%) 40,742 (41.4%) 7,127 (37.7%) 110,699 (54.5%) 5,662 (43.0%) 198,004 (49.3%) 23,565 (39.6%) 0.20 Race ...White; n (%) N/A N/A N/A N/A 151,073 (74.3%) 10,799 (82.1%) 151,073 (74.3%) 10,799 (82.1%) -0.19 ...Black; n (%) N/A N/A N/A N/A 22,905 (11.3%) 916 (7.0%) 22,905 (11.3%) 916 (7.0%) 0.15 ...Asian; n (%) N/A N/A N/A N/A 9,749 (4.8%) 387 (2.9%) 9,749 (4.8%) 387 (2.9%) 0.10 ...Hispanic; n (%) N/A N/A N/A N/A 9,554 (4.7%) 333 (2.5%) 9,554 (4.7%) 333 (2.5%) 0.12 ...North American Native; n (%) N/A N/A N/A N/A 1,385 (0.7%) 58 (0.4%) 1,385 (0.7%) 58 (0.4%) 0.04 ...Other/Unknown; n (%) N/A N/A N/A N/A 8,628 (4.2%) 663 (5.0%) 8,628 (4.2%) 663 (5.0%) -0.04

Region without zero category- United v3 (lumping missing&other category with West) ...Northeast; n (%) 10,960 (11.0%) 2,334 (8.5%) 17,603 (17.9%) 2,575 (13.6%) 38,218 (18.8%) 2,505 (19.0%) 66,781 (16.6%) 7,414 (12.5%) 0.12 ...South; n (%) 52,164 (52.2%) 15,303 (55.9%) 20,254 (20.6%) 3,296 (17.4%) 86,895 (42.7%) 5,524 (42.0%) 159,313 (39.7%) 24,123 (40.6%) -0.02 ...Midwest; n (%) 18,103 (18.1%) 5,373 (19.6%) 50,370 (51.2%) 11,006 (58.2%) 42,468 (20.9%) 2,506 (19.0%) 110,941 (27.6%) 18,885 (31.8%) -0.09 ...West; n (%) 18,676 (18.7%) 4,384 (16.0%) 9,489 (9.6%) 1,978 (10.5%) 35,713 (17.6%) 2,621 (19.9%) 63,878 (15.9%) 8,983 (15.1%) 0.02 ...Unknown+missing; n (%) N/A N/A 629 (0.6%) 57 (0.3%) N/A N/A 629 (0.6%) 57 (0.3%) 0.04 CV Covariates Ischemic heart disease; n (%) 18,990 (19.0%) 5,885 (21.5%) 12,693 (12.9%) 2,535 (13.4%) 54,534 (26.8%) 4,200 (31.9%) 86,217 (21.5%) 12,620 (21.2%) 0.01 Acute MI; n (%) 931 (0.9%) 344 (1.3%) 372 (0.4%) 104 (0.5%) 1,288 (0.6%) 89 (0.7%) 2,591 (0.6%) 537 (0.9%) -0.03 ACS/unstable angina; n (%) 702 (0.7%) 231 (0.8%) 500 (0.5%) 107 (0.6%) 1,499 (0.7%) 118 (0.9%) 2,701 (0.7%) 456 (0.8%) -0.01 Old MI; n (%) 2,549 (2.6%) 819 (3.0%) 906 (0.9%) 191 (1.0%) 5,824 (2.9%) 466 (3.5%) 9,279 (2.3%) 1,476 (2.5%) -0.01 Stable angina; n (%) 3,164 (3.2%) 1,100 (4.0%) 1,545 (1.6%) 382 (2.0%) 6,343 (3.1%) 626 (4.8%) 11,052 (2.8%) 2,108 (3.5%) -0.04

Coronary atherosclerosis and other forms of chronic ischemic heart disease;17,701 n (%)(17.7%) 5,558 (20.3%) 11,987 (12.2%) 2,406 (12.7%) 52,219 (25.7%) 4,074 (31.0%) 81,907 (20.4%) 12,038 (20.2%) 0.00 Other atherosclerosis with ICD10 v2 Copy; n (%) 501 (0.5%) 106 (0.4%) 451 (0.5%) 57 (0.3%) 2,443 (1.2%) 86 (0.7%) 3,395 (0.8%) 249 (0.4%) 0.05

Previous cardiac procedure (CABG or PTCA or Stent) v4; n (%) 407 (0.4%) 189 (0.7%) 212 (0.2%) 52 (0.3%) 461 (0.2%) 55 (0.4%) 1,080 (0.3%) 296 (0.5%) -0.03 History of CABG or PTCA; n (%) 4,493 (4.5%) 1,679 (6.1%) 1,629 (1.7%) 369 (2.0%) 13,342 (6.6%) 1,156 (8.8%) 19,464 (4.8%) 3,204 (5.4%) -0.03 Any stroke; n (%) 4,963 (5.0%) 1,153 (4.2%) 2,035 (2.1%) 273 (1.4%) 10,123 (5.0%) 591 (4.5%) 17,121 (4.3%) 2,017 (3.4%) 0.05

Ischemic stroke (w and w/o mention of cerebral infarction); n (%) 4,899 (4.9%) 1,140 (4.2%) 2,000 (2.0%) 271 (1.4%) 9,999 (4.9%) 585 (4.4%) 16,898 (4.2%) 1,996 (3.4%) 0.04 Hemorrhagic stroke; n (%) 163 (0.2%) 23 (0.1%) 48 (0.0%) 4 (0.0%) 184 (0.1%) 7 (0.1%) 395 (0.1%) 34 (0.1%) 0.00 TIA; n (%) 1,176 (1.2%) 266 (1.0%) 465 (0.5%) 68 (0.4%) 1,913 (0.9%) 98 (0.7%) 3,554 (0.9%) 432 (0.7%) 0.02 Other cerebrovascular disease; n (%) 1,704 (1.7%) 322 (1.2%) 670 (0.7%) 86 (0.5%) 3,962 (1.9%) 236 (1.8%) 6,336 (1.6%) 644 (1.1%) 0.04 Late effects of cerebrovascular disease; n (%) 1,554 (1.6%) 233 (0.9%) 423 (0.4%) 34 (0.2%) 3,186 (1.6%) 107 (0.8%) 5,163 (1.3%) 374 (0.6%) 0.07 Cerebrovascular procedure; n (%) 70 (0.1%) 28 (0.1%) 15 (0.0%) 4 (0.0%) 64 (0.0%) 7 (0.1%) 149 (0.0%) 39 (0.1%) -0.04 Heart failure (CHF); n (%) 6,419 (6.4%) 1,435 (5.2%) 2,935 (3.0%) 399 (2.1%) 18,631 (9.2%) 951 (7.2%) 27,985 (7.0%) 2,785 (4.7%) 0.10

Peripheral Vascular Disease (PVD) or PVD Surgery v2; n (%) 6,638 (6.6%) 1,465 (5.3%) 3,369 (3.4%) 497 (2.6%) 20,972 (10.3%) 1,195 (9.1%) 30,979 (7.7%) 3,157 (5.3%) 0.10 Atrial fibrillation; n (%) 5,807 (5.8%) 1,313 (4.8%) 3,583 (3.6%) 474 (2.5%) 20,723 (10.2%) 1,268 (9.6%) 30,113 (7.5%) 3,055 (5.1%) 0.10 Other cardiac dysrhythmia; n (%) 8,278 (8.3%) 2,142 (7.8%) 4,579 (4.7%) 793 (4.2%) 24,622 (12.1%) 1,806 (13.7%) 37,479 (9.3%) 4,741 (8.0%) 0.05 Cardiac conduction disorders; n (%) 2,246 (2.2%) 580 (2.1%) 1,171 (1.2%) 192 (1.0%) 6,903 (3.4%) 459 (3.5%) 10,320 (2.6%) 1,231 (2.1%) 0.03 Other CVD; n (%) 8,797 (8.8%) 2,259 (8.2%) 5,483 (5.6%) 817 (4.3%) 25,637 (12.6%) 1,671 (12.7%) 39,917 (9.9%) 4,747 (8.0%) 0.07 Diabetes-related complications Diabetic retinopathy; n (%) 6,367 (6.4%) 2,196 (8.0%) 3,371 (3.4%) 764 (4.0%) 14,304 (7.0%) 1,298 (9.9%) 24,042 (6.0%) 4,258 (7.2%) -0.05

Diabetes with other ophthalmic manifestations; n (%) 904 (0.9%) 230 (0.8%) 1,868 (1.9%) 305 (1.6%) 4,906 (2.4%) 267 (2.0%) 7,678 (1.9%) 802 (1.3%) 0.05

Retinal detachment, vitreous hemorrhage, vitrectomy; n (%) 415 (0.4%) 135 (0.5%) 328 (0.3%) 76 (0.4%) 780 (0.4%) 80 (0.6%) 1,523 (0.4%) 291 (0.5%) -0.01 Retinal laser coagulation therapy; n (%) 560 (0.6%) 158 (0.6%) 504 (0.5%) 115 (0.6%) 1,220 (0.6%) 74 (0.6%) 2,284 (0.6%) 347 (0.6%) 0.00 Occurrence of Diabetic Neuropathy v2 Copy; n (%) 19,198 (19.2%) 5,771 (21.1%) 10,496 (10.7%) 2,631 (13.9%) 39,771 (19.6%) 3,284 (25.0%) 69,465 (17.3%) 11,686 (19.7%) -0.06

Occurrence of diabetic nephropathy V3 with ICD10 Copy; n (%) 15,429 (15.4%) 3,259 (11.9%) 6,218 (6.3%) 1,309 (6.9%) 22,695 (11.2%) 1,478 (11.2%) 44,342 (11.0%) 6,046 (10.2%) 0.03 Hypoglycemia v2; n (%) 1,757 (1.8%) 141 (0.5%) 1,705 (1.7%) 183 (1.0%) 4,423 (2.2%) 107 (0.8%) 7,885 (2.0%) 431 (0.7%) 0.11 Hyperglycemia; n (%) 4,186 (4.2%) 1,098 (4.0%) 3,136 (3.2%) 518 (2.7%) 8,064 (4.0%) 466 (3.5%) 15,386 (3.8%) 2,082 (3.5%) 0.02

Disorders of fluid electrolyte and acid-base balance; n (%) 6,080 (6.1%) 1,099 (4.0%) 3,203 (3.3%) 434 (2.3%) 12,731 (6.3%) 479 (3.6%) 22,014 (5.5%) 2,012 (3.4%) 0.10 Diabetic ketoacidosis; n (%) 385 (0.4%) 76 (0.3%) 309 (0.3%) 47 (0.2%) 668 (0.3%) 22 (0.2%) 1,362 (0.3%) 145 (0.2%) 0.02

Hyperosmolar hyperglycemic nonketotic syndrome (HONK); n (%) 589 (0.6%) 166 (0.6%) 468 (0.5%) 92 (0.5%) 1,077 (0.5%) 80 (0.6%) 2,134 (0.5%) 338 (0.6%) -0.01

Diabetes with peripheral circulatory disorders with ICD-10 v2 Copy; n (%)7,150 (7.2%) 1,909 (7.0%) 2,798 (2.8%) 630 (3.3%) 15,464 (7.6%) 1,122 (8.5%) 25,412 (6.3%) 3,661 (6.2%) 0.00 Diabetic Foot; n (%) 1,967 (2.0%) 591 (2.2%) 1,422 (1.4%) 320 (1.7%) 4,932 (2.4%) 286 (2.2%) 8,321 (2.1%) 1,197 (2.0%) 0.01 Gangrene v2; n (%) 235 (0.2%) 63 (0.2%) 144 (0.1%) 28 (0.1%) 380 (0.2%) 33 (0.3%) 759 (0.2%) 124 (0.2%) 0.00 Lower extremity amputation; n (%) 644 (0.6%) 207 (0.8%) 256 (0.3%) 66 (0.3%) 1,155 (0.6%) 81 (0.6%) 2,055 (0.5%) 354 (0.6%) -0.01 Osteomyelitis; n (%) 491 (0.5%) 155 (0.6%) 361 (0.4%) 78 (0.4%) 936 (0.5%) 54 (0.4%) 1,788 (0.4%) 287 (0.5%) -0.01 Skin infections v2; n (%) 4,914 (4.9%) 1,384 (5.1%) 4,428 (4.5%) 886 (4.7%) 11,729 (5.8%) 781 (5.9%) 21,071 (5.2%) 3,051 (5.1%) 0.00 Erectile dysfunction; n (%) 2,938 (2.9%) 1,188 (4.3%) 2,680 (2.7%) 585 (3.1%) 4,367 (2.1%) 501 (3.8%) 9,985 (2.5%) 2,274 (3.8%) -0.07 Diabetes with unspecified complication; n (%) 5,922 (5.9%) 1,946 (7.1%) 4,818 (4.9%) 1,306 (6.9%) 11,396 (5.6%) 953 (7.2%) 22,136 (5.5%) 4,205 (7.1%) -0.07

Diabetes mellitus without mention of complications; n (%) 82,871 (83.0%) 21,178 (77.3%) 86,660 (88.1%) 15,269 (80.7%) 184,478 (90.7%) 11,109 (84.4%) 354,009 (88.2%) 47,556 (80.0%) 0.23

Hypertension: 1 inpatient or 2 outpatient claims within 365 days; n (%)84,740 (84.8%) 23,304 (85.1%) 75,314 (76.6%) 14,637 (77.4%) 185,875 (91.4%) 11,981 (91.1%) 345,929 (86.2%) 49,922 (84.0%) 0.06 Hyperlipidemia v2; n (%) 70,468 (70.5%) 19,569 (71.4%) 65,929 (67.0%) 13,478 (71.3%) 154,166 (75.8%) 10,169 (77.3%) 290,563 (72.4%) 43,216 (72.7%) -0.01 Edema; n (%) 5,273 (5.3%) 1,202 (4.4%) 2,878 (2.9%) 467 (2.5%) 16,056 (7.9%) 876 (6.7%) 24,207 (6.0%) 2,545 (4.3%) 0.08 Renal Dysfunction (non-diabetic) v2; n (%) 19,582 (19.6%) 3,179 (11.6%) 8,494 (8.6%) 958 (5.1%) 42,497 (20.9%) 1,822 (13.8%) 70,573 (17.6%) 5,959 (10.0%) 0.22 Occurrence of acute renal disease v2; n (%) 2,581 (2.6%) 332 (1.2%) 1,243 (1.3%) 80 (0.4%) 5,423 (2.7%) 130 (1.0%) 9,247 (2.3%) 542 (0.9%) 0.11 Occurrence of chronic renal insufficiency; n (%) 16,369 (16.4%) 2,354 (8.6%) 6,265 (6.4%) 657 (3.5%) 36,061 (17.7%) 1,453 (11.0%) 58,695 (14.6%) 4,464 (7.5%) 0.23 Chronic kidney disease v2; n (%) 15,864 (15.9%) 2,270 (8.3%) 5,871 (6.0%) 615 (3.3%) 34,532 (17.0%) 1,391 (10.6%) 56,267 (14.0%) 4,276 (7.2%) 0.22 CKD Stage 3-4; n (%) 10,687 (10.7%) 1,245 (4.5%) 3,761 (3.8%) 303 (1.6%) 24,060 (11.8%) 839 (6.4%) 38,508 (9.6%) 2,387 (4.0%) 0.22 Occurrence of hypertensive nephropathy; n (%) 6,766 (6.8%) 968 (3.5%) 2,293 (2.3%) 229 (1.2%) 13,584 (6.7%) 526 (4.0%) 22,643 (5.6%) 1,723 (2.9%) 0.13

Occurrence of miscellaneous renal insufficiency v2; n (%) 4,400 (4.4%) 874 (3.2%) 2,417 (2.5%) 271 (1.4%) 11,162 (5.5%) 523 (4.0%) 17,979 (4.5%) 1,668 (2.8%) 0.09 Glaucoma or cataracts v2; n (%) 18,320 (18.3%) 4,419 (16.1%) 12,973 (13.2%) 2,270 (12.0%) 54,403 (26.8%) 3,639 (27.7%) 85,696 (21.3%) 10,328 (17.4%) 0.10 Cellulitis or abscess of toe; n (%) 1,284 (1.3%) 391 (1.4%) 849 (0.9%) 225 (1.2%) 2,592 (1.3%) 237 (1.8%) 4,725 (1.2%) 853 (1.4%) -0.02 Foot ulcer; n (%) 1,877 (1.9%) 539 (2.0%) 1,377 (1.4%) 296 (1.6%) 4,802 (2.4%) 270 (2.1%) 8,056 (2.0%) 1,105 (1.9%) 0.01 Bladder stones; n (%) 125 (0.1%) 27 (0.1%) 71 (0.1%) 11 (0.1%) 307 (0.2%) 17 (0.1%) 503 (0.1%) 55 (0.1%) 0.00 Kidney stones; n (%) 1,974 (2.0%) 533 (1.9%) 1,775 (1.8%) 310 (1.6%) 4,540 (2.2%) 294 (2.2%) 8,289 (2.1%) 1,137 (1.9%) 0.01 Urinary tract infections (UTIs); n (%) 7,752 (7.8%) 1,339 (4.9%) 4,684 (4.8%) 565 (3.0%) 23,016 (11.3%) 885 (6.7%) 35,452 (8.8%) 2,789 (4.7%) 0.16 Dipstick urinalysis; n (%) 34,548 (34.6%) 8,269 (30.2%) 29,300 (29.8%) 5,259 (27.8%) 76,034 (37.4%) 4,496 (34.2%) 139,882 (34.8%) 18,024 (30.3%) 0.10 Non-dipstick urinalysis; n (%) 43,363 (43.4%) 12,648 (46.2%) 36,411 (37.0%) 8,432 (44.6%) 84,136 (41.4%) 6,319 (48.0%) 163,910 (40.8%) 27,399 (46.1%) -0.11 Urine function test; n (%) 1,897 (1.9%) 418 (1.5%) 1,625 (1.7%) 200 (1.1%) 6,250 (3.1%) 434 (3.3%) 9,772 (2.4%) 1,052 (1.8%) 0.04 Cytology; n (%) 560 (0.6%) 117 (0.4%) 522 (0.5%) 60 (0.3%) 1,497 (0.7%) 67 (0.5%) 2,579 (0.6%) 244 (0.4%) 0.03 Cystoscopy; n (%) 843 (0.8%) 204 (0.7%) 726 (0.7%) 103 (0.5%) 2,199 (1.1%) 129 (1.0%) 3,768 (0.9%) 436 (0.7%) 0.02 Other Covariates Liver disease; n (%) 3,416 (3.4%) 1,355 (4.9%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 3,416 (0.9%) 1,355 (2.3%) -0.11 Osteoarthritis; n (%) 14,159 (14.2%) 3,503 (12.8%) 8,944 (9.1%) 1,459 (7.7%) 41,716 (20.5%) 2,523 (19.2%) 64,819 (16.1%) 7,485 (12.6%) 0.10

Other arthritis, arthropathies and musculoskeletal pain; n (%) 33,077 (33.1%) 8,620 (31.5%) 26,598 (27.0%) 4,912 (26.0%) 82,377 (40.5%) 4,956 (37.7%) 142,052 (35.4%) 18,488 (31.1%) 0.09 Dorsopathies; n (%) 20,631 (20.7%) 5,759 (21.0%) 15,907 (16.2%) 3,084 (16.3%) 48,687 (23.9%) 3,203 (24.3%) 85,225 (21.2%) 12,046 (20.3%) 0.02 Fractures; n (%) 2,412 (2.4%) 501 (1.8%) 1,716 (1.7%) 279 (1.5%) 6,339 (3.1%) 342 (2.6%) 10,467 (2.6%) 1,122 (1.9%) 0.05 Falls v2; n (%) 3,187 (3.2%) 522 (1.9%) 965 (1.0%) 123 (0.7%) 7,872 (3.9%) 346 (2.6%) 12,024 (3.0%) 991 (1.7%) 0.09 Osteoporosis; n (%) 4,316 (4.3%) 634 (2.3%) 1,543 (1.6%) 149 (0.8%) 15,070 (7.4%) 631 (4.8%) 20,929 (5.2%) 1,414 (2.4%) 0.15 Hyperthyroidism; n (%) 588 (0.6%) 179 (0.7%) 466 (0.5%) 85 (0.4%) 1,690 (0.8%) 99 (0.8%) 2,744 (0.7%) 363 (0.6%) 0.01 Hypothyroidism v2; n (%) 13,829 (13.8%) 3,532 (12.9%) 10,304 (10.5%) 2,178 (11.5%) 21,523 (10.6%) 946 (7.2%) 45,656 (11.4%) 6,656 (11.2%) 0.01 Other disorders of thyroid gland V2; n (%) 3,455 (3.5%) 1,215 (4.4%) 2,934 (3.0%) 902 (4.8%) 7,712 (3.8%) 667 (5.1%) 14,101 (3.5%) 2,784 (4.7%) -0.06 Depression; n (%) 7,320 (7.3%) 1,821 (6.6%) 5,335 (5.4%) 914 (4.8%) 17,919 (8.8%) 902 (6.9%) 30,574 (7.6%) 3,637 (6.1%) 0.06 Anxiety; n (%) 7,953 (8.0%) 2,396 (8.7%) 5,309 (5.4%) 1,125 (5.9%) 15,687 (7.7%) 995 (7.6%) 28,949 (7.2%) 4,516 (7.6%) -0.02 Sleep_Disorder; n (%) 3,987 (4.0%) 673 (2.5%) 5,785 (5.9%) 766 (4.1%) 11,002 (5.4%) 418 (3.2%) 20,774 (5.2%) 1,857 (3.1%) 0.11 Dementia; n (%) 3,796 (3.8%) 361 (1.3%) 1,343 (1.4%) 91 (0.5%) 14,445 (7.1%) 369 (2.8%) 19,584 (4.9%) 821 (1.4%) 0.20 Delirium; n (%) 1,038 (1.0%) 110 (0.4%) 410 (0.4%) 31 (0.2%) 2,997 (1.5%) 80 (0.6%) 4,445 (1.1%) 221 (0.4%) 0.08 Psychosis; n (%) 1,115 (1.1%) 171 (0.6%) 403 (0.4%) 36 (0.2%) 3,561 (1.8%) 67 (0.5%) 5,079 (1.3%) 274 (0.5%) 0.08 Obesity; n (%) 17,544 (17.6%) 7,711 (28.1%) 6,568 (6.7%) 1,684 (8.9%) 10,068 (5.0%) 806 (6.1%) 34,180 (8.5%) 10,201 (17.2%) -0.26 Overweight; n (%) 7,117 (7.1%) 2,123 (7.7%) 3,068 (3.1%) 700 (3.7%) 8,443 (4.2%) 650 (4.9%) 18,628 (4.6%) 3,473 (5.8%) -0.05 Smoking; n (%) 10,562 (10.6%) 3,243 (11.8%) 4,864 (4.9%) 882 (4.7%) 21,088 (10.4%) 1,434 (10.9%) 36,514 (9.1%) 5,559 (9.3%) -0.01 Alcohol abuse or dependence; n (%) 685 (0.7%) 199 (0.7%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) #VALUE! 199 (0.3%) #VALUE! Drug abuse or dependence; n (%) 1,133 (1.1%) 359 (1.3%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1,133 (0.3%) 359 (0.6%) -0.04 COPD; n (%) 6,952 (7.0%) 1,485 (5.4%) 3,056 (3.1%) 386 (2.0%) 17,808 (8.8%) 895 (6.8%) 27,816 (6.9%) 2,766 (4.7%) 0.09 Asthma; n (%) 4,622 (4.6%) 1,225 (4.5%) 3,363 (3.4%) 592 (3.1%) 9,980 (4.9%) 656 (5.0%) 17,965 (4.5%) 2,473 (4.2%) 0.01 Obstructive sleep apnea; n (%) 7,880 (7.9%) 3,326 (12.1%) 7,903 (8.0%) 2,046 (10.8%) 10,766 (5.3%) 1,274 (9.7%) 26,549 (6.6%) 6,646 (11.2%) -0.16 Pneumonia; n (%) 1,745 (1.7%) 319 (1.2%) 1,136 (1.2%) 158 (0.8%) 4,422 (2.2%) 214 (1.6%) 7,303 (1.8%) 691 (1.2%) 0.05 Imaging; n (%) 73 (0.1%) 17 (0.1%) 17 (0.0%) 4 (0.0%) 135 (0.1%) 10 (0.1%) 225 (0.1%) 31 (0.1%) 0.00 Diabetes Medications DM Medications - AGIs; n (%) 499 (0.5%) 97 (0.4%) 310 (0.3%) 64 (0.3%) 1,243 (0.6%) 58 (0.4%) 2,052 (0.5%) 219 (0.4%) 0.01 DM Medications - Glitazones; n (%) 7,594 (7.6%) 2,318 (8.5%) 6,881 (7.0%) 1,520 (8.0%) 14,722 (7.2%) 1,253 (9.5%) 29,197 (7.3%) 5,091 (8.6%) -0.05 DM Medications - GLP-1 RA; n (%) 4,184 (4.2%) 5,850 (21.4%) 4,354 (4.4%) 4,829 (25.5%) 5,290 (2.6%) 2,529 (19.2%) 13,828 (3.4%) 13,208 (22.2%) -0.59 DM Medications - Insulin; n (%) 17,835 (17.9%) 7,838 (28.6%) 14,817 (15.1%) 5,867 (31.0%) 39,115 (19.2%) 4,548 (34.6%) 71,767 (17.9%) 18,253 (30.7%) -0.30 DM Medications - Meglitinides; n (%) 1,041 (1.0%) 212 (0.8%) 1,089 (1.1%) 171 (0.9%) 3,580 (1.8%) 247 (1.9%) 5,710 (1.4%) 630 (1.1%) 0.03 DM Medications - Metformin; n (%) 74,681 (74.8%) 20,362 (74.3%) 79,574 (80.9%) 14,355 (75.9%) 142,034 (69.9%) 9,591 (72.9%) 296,289 (73.8%) 44,308 (74.5%) -0.02

Concomitant initiation or current use of 2nd Generation SUs; n (%) 33,222 (33.3%) 7,632 (27.9%) 29,037 (29.5%) 4,720 (25.0%) 73,210 (36.0%) 4,236 (32.2%) 135,469 (33.7%) 16,588 (27.9%) 0.13 Concomitant initiation or current use of AGIs; n (%) 359 (0.4%) 65 (0.2%) 216 (0.2%) 39 (0.2%) 888 (0.4%) 35 (0.3%) 1,463 (0.4%) 139 (0.2%) 0.04

Concomitant initiation or current use of Glitazones; n (%) 6,052 (6.1%) 1,790 (6.5%) 5,547 (5.6%) 1,221 (6.5%) 11,634 (5.7%) 990 (7.5%) 23,233 (5.8%) 4,001 (6.7%) -0.04

Concomitant initiation or current use of GLP-1 RA; n (%) 2,392 (2.4%) 4,382 (16.0%) 2,527 (2.6%) 3,730 (19.7%) 2,849 (1.4%) 1,906 (14.5%) 7,768 (1.9%) 10,018 (16.8%) -0.53

Concomitant initiation or current use of Insulin; n (%) 13,381 (13.4%) 5,986 (21.9%) 11,021 (11.2%) 4,466 (23.6%) 29,957 (14.7%) 3,603 (27.4%) 54,359 (13.5%) 14,055 (23.6%) -0.26

Concomitant initiation or current use of Meglitinides; n (%) 773 (0.8%) 145 (0.5%) 768 (0.8%) 117 (0.6%) 2,607 (1.3%) 170 (1.3%) 4,148 (1.0%) 432 (0.7%) 0.03

Concomitant initiation or current use of Metformin; n (%) 64,669 (64.7%) 16,561 (60.5%) 70,407 (71.6%) 11,825 (62.5%) 122,594 (60.3%) 8,039 (61.1%) 257,670 (64.2%) 36,425 (61.3%) 0.06 Past use of 2nd Generation SUs Copy; n (%) 7,266 (7.3%) 2,028 (7.4%) 6,956 (7.1%) 1,253 (6.6%) 14,813 (7.3%) 902 (6.9%) 29,035 (7.2%) 4,183 (7.0%) 0.01 Past use of AGIs Copy; n (%) 140 (0.1%) 32 (0.1%) 94 (0.1%) 25 (0.1%) 355 (0.2%) 23 (0.2%) 589 (0.1%) 80 (0.1%) 0.00 Past use of Glitazones Copy; n (%) 1,542 (1.5%) 528 (1.9%) 1,334 (1.4%) 299 (1.6%) 3,088 (1.5%) 263 (2.0%) 5,964 (1.5%) 1,090 (1.8%) -0.02 Past use of GLP-1 RA Copy; n (%) 1,977 (2.0%) 1,701 (6.2%) 2,007 (2.0%) 1,253 (6.6%) 2,441 (1.2%) 623 (4.7%) 6,425 (1.6%) 3,577 (6.0%) -0.23 Past use of Insulin Copy; n (%) 4,454 (4.5%) 1,852 (6.8%) 3,797 (3.9%) 1,401 (7.4%) 9,160 (4.5%) 945 (7.2%) 17,411 (4.3%) 4,198 (7.1%) -0.12 Past use of Meglitinides Copy; n (%) 268 (0.3%) 67 (0.2%) 321 (0.3%) 54 (0.3%) 973 (0.5%) 77 (0.6%) 1,562 (0.4%) 198 (0.3%) 0.02 Past use of metformin (final) Copy; n (%) 10,012 (10.0%) 3,801 (13.9%) 9,167 (9.3%) 2,530 (13.4%) 19,440 (9.6%) 1,552 (11.8%) 38,619 (9.6%) 7,883 (13.3%) -0.12 Other Medications Use of ACE inhibitors; n (%) 52,616 (52.7%) 14,800 (54.0%) 52,849 (53.7%) 10,492 (55.5%) 96,076 (47.3%) 6,205 (47.2%) 201,541 (50.2%) 31,497 (53.0%) -0.06 Use of ARBs; n (%) 33,459 (33.5%) 9,268 (33.8%) 32,714 (33.3%) 6,489 (34.3%) 69,748 (34.3%) 4,833 (36.7%) 135,921 (33.8%) 20,590 (34.6%) -0.02 Use of Loop Diuretics - United; n (%) 10,502 (10.5%) 2,316 (8.5%) 6,912 (7.0%) 1,075 (5.7%) 33,131 (16.3%) 1,744 (13.3%) 50,545 (12.6%) 5,135 (8.6%) 0.13 Use of other diuretics- United; n (%) 2,623 (2.6%) 833 (3.0%) 2,133 (2.2%) 453 (2.4%) 6,785 (3.3%) 483 (3.7%) 11,541 (2.9%) 1,769 (3.0%) -0.01 Use of nitrates-United; n (%) 4,760 (4.8%) 1,425 (5.2%) 3,232 (3.3%) 624 (3.3%) 14,468 (7.1%) 976 (7.4%) 22,460 (5.6%) 3,025 (5.1%) 0.02 Use of other hypertension drugs; n (%) 6,251 (6.3%) 1,267 (4.6%) 4,450 (4.5%) 643 (3.4%) 15,746 (7.7%) 809 (6.1%) 26,447 (6.6%) 2,719 (4.6%) 0.09 Use of digoxin- United; n (%) 1,351 (1.4%) 278 (1.0%) 1,001 (1.0%) 112 (0.6%) 5,685 (2.8%) 306 (2.3%) 8,037 (2.0%) 696 (1.2%) 0.06 Use of Anti-arrhythmics; n (%) 1,058 (1.1%) 283 (1.0%) 807 (0.8%) 143 (0.8%) 3,770 (1.9%) 218 (1.7%) 5,635 (1.4%) 644 (1.1%) 0.03 Use of COPD/asthma meds- United; n (%) 14,067 (14.1%) 3,637 (13.3%) 12,756 (13.0%) 2,412 (12.8%) 32,384 (15.9%) 2,112 (16.1%) 59,207 (14.7%) 8,161 (13.7%) 0.03 Use of statins; n (%) 71,183 (71.3%) 20,272 (74.0%) 65,053 (66.1%) 13,377 (70.7%) 148,529 (73.1%) 10,331 (78.5%) 284,765 (70.9%) 43,980 (74.0%) -0.07 Use of other lipid-lowering drugs; n (%) 11,144 (11.2%) 3,351 (12.2%) 12,301 (12.5%) 2,743 (14.5%) 24,891 (12.2%) 1,915 (14.6%) 48,336 (12.0%) 8,009 (13.5%) -0.04 Use of antiplatelet agents; n (%) 12,026 (12.0%) 3,756 (13.7%) 10,435 (10.6%) 2,047 (10.8%) 30,403 (15.0%) 2,275 (17.3%) 52,864 (13.2%) 8,078 (13.6%) -0.01

Use of oral anticoagulants (Dabigatran, Rivaroxaban, Apixaban, Warfarin);5,155 n (%) (5.2%) 1,283 (4.7%) 3,619 (3.7%) 581 (3.1%) 17,505 (8.6%) 1,132 (8.6%) 26,279 (6.5%) 2,996 (5.0%) 0.06

Use of heparin and other low-molecular weight heparins; n (%) 198 (0.2%) 43 (0.2%) 9 (0.0%) 1 (0.0%) 420 (0.2%) 21 (0.2%) 627 (0.2%) 065 (0.1%) 0.03 Use of NSAIDs; n (%) 16,220 (16.2%) 4,517 (16.5%) 16,087 (16.4%) 3,178 (16.8%) 32,311 (15.9%) 1,975 (15.0%) 64,618 (16.1%) 9,670 (16.3%) -0.01 Use of oral corticosteroids; n (%) 10,445 (10.5%) 2,832 (10.3%) 9,420 (9.6%) 1,722 (9.1%) 23,684 (11.7%) 1,501 (11.4%) 43,549 (10.8%) 6,055 (10.2%) 0.02 Use of bisphosphonate (United); n (%) 2,212 (2.2%) 322 (1.2%) 803 (0.8%) 70 (0.4%) 6,829 (3.4%) 252 (1.9%) 9,844 (2.5%) 644 (1.1%) 0.11 Use of opioids- United; n (%) 20,346 (20.4%) 5,472 (20.0%) 18,620 (18.9%) 3,581 (18.9%) 42,529 (20.9%) 2,588 (19.7%) 81,495 (20.3%) 11,641 (19.6%) 0.02 Use of antidepressants; n (%) 22,602 (22.6%) 6,573 (24.0%) 19,480 (19.8%) 4,303 (22.8%) 48,867 (24.0%) 3,160 (24.0%) 90,949 (22.6%) 14,036 (23.6%) -0.02 Use of antipsychotics; n (%) 2,584 (2.6%) 556 (2.0%) 1,381 (1.4%) 263 (1.4%) 6,338 (3.1%) 258 (2.0%) 10,303 (2.6%) 1,077 (1.8%) 0.05 Use of anticonvulsants; n (%) 16,330 (16.3%) 4,552 (16.6%) 10,690 (10.9%) 2,193 (11.6%) 34,272 (16.9%) 2,157 (16.4%) 61,292 (15.3%) 8,902 (15.0%) 0.01 Use of lithium- United; n (%) 147 (0.1%) 39 (0.1%) 115 (0.1%) 29 (0.2%) 242 (0.1%) 9 (0.1%) 504 (0.1%) 077 (0.1%) 0.00 Use of Benzos- United; n (%) 9,376 (9.4%) 2,472 (9.0%) 7,846 (8.0%) 1,587 (8.4%) 21,369 (10.5%) 1,277 (9.7%) 38,591 (9.6%) 5,336 (9.0%) 0.02 Use of anxiolytics/hypnotics- United; n (%) 4,899 (4.9%) 1,421 (5.2%) 5,117 (5.2%) 1,058 (5.6%) 10,049 (4.9%) 683 (5.2%) 20,065 (5.0%) 3,162 (5.3%) -0.01 Use of dementia meds- United; n (%) 2,332 (2.3%) 208 (0.8%) 1,003 (1.0%) 51 (0.3%) 10,424 (5.1%) 272 (2.1%) 13,759 (3.4%) 531 (0.9%) 0.17 Use of antiparkinsonian meds- United; n (%) 2,112 (2.1%) 562 (2.1%) 1,514 (1.5%) 265 (1.4%) 6,081 (3.0%) 335 (2.5%) 9,707 (2.4%) 1,162 (2.0%) 0.03 Any use of pramlintide; n (%) 2 (0.0%) 9 (0.0%) 9 (0.0%) 23 (0.1%) 18 (0.0%) 6 (0.0%) 029 (0.0%) 038 (0.1%) -0.04 Any use of 1st generation sulfonylureas; n (%) 2 (0.0%) 1 (0.0%) 10 (0.0%) 1 (0.0%) 16 (0.0%) 1 (0.0%) 028 (0.0%) 003 (0.0%) 0.00 Entresto (sacubitril/valsartan); n (%) 158 (0.2%) 122 (0.4%) 52 (0.1%) 22 (0.1%) 158 (0.1%) 43 (0.3%) 368 (0.1%) 187 (0.3%) 0.00 Initiation as monotherapy v4 Copy; n (%) 85,916 (86.0%) 25,773 (94.1%) 84,176 (85.6%) 17,936 (94.8%) 184,924 (91.0%) 12,565 (95.5%) 355,016 (88.4%) 56,274 (94.6%) -0.22 Labs 198,248 46,306 Lab values- HbA1c (%) v3; n (%) 43,141 (43.2%) 11,298 (41.2%) 6,423 (6.5%) 1,049 (5.5%) N/A N/A 49,564 (25.0%) 12,347 (26.7%) -0.04 Lab values- HbA1c (%) (within 3 months) v3; n (%) 34,616 (34.6%) 9,068 (33.1%) 5,174 (5.3%) 858 (4.5%) N/A N/A 39,790 (20.1%) 9,926 (21.4%) -0.03 Lab values- HbA1c (%) (within 6 months) v3; n (%) 43,141 (43.2%) 11,298 (41.2%) 6,423 (6.5%) 1,049 (5.5%) N/A N/A 49,564 (25.0%) 12,347 (26.7%) -0.04 Lab values- BNP; n (%) 749 (0.7%) 156 (0.6%) 74 (0.1%) 5 (0.0%) N/A N/A 823 (0.4%) 161 (0.3%) 0.02 Lab values- BNP (within 3 months); n (%) 463 (0.5%) 98 (0.4%) 53 (0.1%) 1 (0.0%) N/A N/A 516 (0.3%) 099 (0.2%) 0.02 Lab values- BNP (within 6 months); n (%) 749 (0.7%) 156 (0.6%) 74 (0.1%) 5 (0.0%) N/A N/A 823 (0.4%) 161 (0.3%) 0.02 Lab values- BUN (mg/dl); n (%) 42,226 (42.3%) 10,947 (40.0%) 6,201 (6.3%) 967 (5.1%) N/A N/A 48,427 (24.4%) 11,914 (25.7%) -0.03 Lab values- BUN (mg/dl) (within 3 months); n (%) 33,174 (33.2%) 8,603 (31.4%) 4,838 (4.9%) 783 (4.1%) N/A N/A 38,012 (19.2%) 9,386 (20.3%) -0.03 Lab values- BUN (mg/dl) (within 6 months); n (%) 42,226 (42.3%) 10,947 (40.0%) 6,201 (6.3%) 967 (5.1%) N/A N/A 48,427 (24.4%) 11,914 (25.7%) -0.03 Lab values- Creatinine (mg/dl) v2; n (%) 43,684 (43.7%) 11,561 (42.2%) 6,653 (6.8%) 1,095 (5.8%) N/A N/A 50,337 (25.4%) 12,656 (27.3%) -0.04

Lab values- Creatinine (mg/dl) (within 3 months) v2; n (%) 34,353 (34.4%) 9,066 (33.1%) 5,215 (5.3%) 882 (4.7%) N/A N/A 39,568 (20.0%) 9,948 (21.5%) -0.04

Lab values- Creatinine (mg/dl) (within 6 months) v2; n (%) 43,684 (43.7%) 11,561 (42.2%) 6,653 (6.8%) 1,095 (5.8%) N/A N/A 50,337 (25.4%) 12,656 (27.3%) -0.04 Lab values- HDL level (mg/dl); n (%) 36,599 (36.6%) 9,688 (35.4%) 5,867 (6.0%) 1,004 (5.3%) N/A N/A 42,466 (21.4%) 10,692 (23.1%) -0.04

Lab values- HDL level (mg/dl) (within 3 months); n (%) 27,311 (27.3%) 7,215 (26.3%) 4,458 (4.5%) 768 (4.1%) N/A N/A 31,769 (16.0%) 7,983 (17.2%) -0.03

Lab values- HDL level (mg/dl) (within 6 months); n (%) 36,599 (36.6%) 9,688 (35.4%) 5,867 (6.0%) 1,004 (5.3%) N/A N/A 42,466 (21.4%) 10,692 (23.1%) -0.04 Lab values- LDL level (mg/dl) v2; n (%) 37,864 (37.9%) 10,005 (36.5%) 6,037 (6.1%) 991 (5.2%) N/A N/A 43,901 (22.1%) 10,996 (23.7%) -0.04

Lab values- LDL level (mg/dl) (within 3 months) v2; n (%) 28,216 (28.2%) 7,452 (27.2%) 4,563 (4.6%) 765 (4.0%) N/A N/A 32,779 (16.5%) 8,217 (17.7%) -0.03

Lab values- LDL level (mg/dl) (within 6 months) v2; n (%) 37,864 (37.9%) 10,005 (36.5%) 6,037 (6.1%) 991 (5.2%) N/A N/A 43,901 (22.1%) 10,996 (23.7%) -0.04 Lab values- NT-proBNP; n (%) 114 (0.1%) 43 (0.2%) 17 (0.0%) 2 (0.0%) N/A N/A 131 (0.1%) 45 (0.1%) 0.00 Lab values- NT-proBNP (within 3 months); n (%) 66 (0.1%) 27 (0.1%) 12 (0.0%) 2 (0.0%) N/A N/A 78 (0.0%) 29 (0.1%) - Lab values- NT-proBNP (within 6 months); n (%) 114 (0.1%) 43 (0.2%) 17 (0.0%) 2 (0.0%) N/A N/A 131 (0.1%) 45 (0.1%) - Lab values- Total cholesterol (mg/dl) v2; n (%) 37,177 (37.2%) 9,915 (36.2%) 5,903 (6.0%) 1,018 (5.4%) N/A N/A 43,080 (21.7%) 10,933 (23.6%) -0.05

Lab values- Total cholesterol (mg/dl) (within 3 months) v2; n (%) 27,768 (27.8%) 7,384 (27.0%) 4,489 (4.6%) 783 (4.1%) N/A N/A 32,257 (16.3%) 8,167 (17.6%) -0.03

Lab values- Total cholesterol (mg/dl) (within 6 months) v2; n (%) 37,177 (37.2%) 9,915 (36.2%) 5,903 (6.0%) 1,018 (5.4%) N/A N/A 43,080 (21.7%) 10,933 (23.6%) -0.05 Lab values- Triglyceride level (mg/dl); n (%) 36,829 (36.9%) 9,848 (35.9%) 5,814 (5.9%) 1,000 (5.3%) N/A N/A 42,643 (21.5%) 10,848 (23.4%) -0.05

Lab values- Triglyceride level (mg/dl) (within 3 months); n (%) 27,527 (27.6%) 7,338 (26.8%) 4,418 (4.5%) 771 (4.1%) N/A N/A 31,945 (16.1%) 8,109 (17.5%) -0.04

Lab values- Triglyceride level (mg/dl) (within 6 months); n (%) 36,829 (36.9%) 9,848 (35.9%) 5,814 (5.9%) 1,000 (5.3%) N/A N/A 42,643 (21.5%) 10,848 (23.4%) -0.05

Lab result number- HbA1c (%) mean (only 2 to 20 included) v4 42,905 11,242 6,311 1,018 N/A N/A 49,216 12,260 ...mean (sd) 8.36 (1.78) 8.55 (1.75) 8.53 (1.88) 8.32 (1.79) N/A N/A 8.38 (1.79) 8.53 (1.75) -0.08 ...median [IQR] 8.00 [7.15, 9.25] 8.20 [7.30, 9.55] 8.05 [7.15, 9.50] 8.00 [7.00, 9.00] N/A N/A 8.01 (1.79) 8.18 (1.75) -0.10 ...Missing; n (%) 56,998 (57.1%) 16,152 (59.0%) 92,034 (93.6%) 17,894 (94.6%) N/A N/A 149,032 (75.2%) 34,046 (73.5%) 0.04 Lab result number- BNP mean v2 749 156 74 5 N/A N/A 823 161 ...mean (sd) 154.93 (290.29) 146.64 (514.40) 3,931.76 (32,532.43) 32.60 (34.74) N/A N/A 494.52 (9710.65) 143.10 (509.52) 0.05 ...median [IQR] 65.20 [25.55, 167.50] 34.45 [14.55, 89.70] 76.50 [29.75, 193.00] 18.00 [13.50, 59.00] N/A N/A #VALUE! #VALUE! #VALUE! ...Missing; n (%) 99,154 (99.3%) 27,238 (99.4%) 98,271 (99.9%) 18,907 (100.0%) N/A N/A 197,425 (99.6%) 46,145 (99.7%) -0.02 Lab result number- BUN (mg/dl) mean v2 42,226 10,947 6,201 967 N/A N/A 48,427 11,914 ...mean (sd) 17.98 (7.45) 16.64 (5.62) 1,795.05 (17,168.60) 2,184.17 (18,571.33) N/A N/A 245.53 (6143.29) 192.57 (5288.81) 0.01 ...median [IQR] 16.50 [13.00, 21.00] 16.00 [13.00, 19.50] 16.00 [13.00, 20.00] 15.50 [13.00, 19.00] N/A N/A #VALUE! #VALUE! #VALUE! ...Missing; n (%) 57,677 (57.7%) 16,447 (60.0%) 92,144 (93.7%) 17,945 (94.9%) N/A N/A 149,821 (75.6%) 34,392 (74.3%) 0.03

Lab result number- Creatinine (mg/dl) mean (only 0.1 to 15 included) v3 43,333 11,484 5,645 711 N/A N/A 48,978 12,195 ...mean (sd) 1.01 (0.39) 0.92 (0.24) 0.98 (0.33) 0.94 (0.20) N/A N/A 1.01 (0.38) 0.92 (0.24) 0.28 ...median [IQR] 0.93 [0.78, 1.15] 0.89 [0.75, 1.05] 0.95 [0.79, 1.08] 0.95 [0.81, 1.00] N/A N/A 0.93 (0.38) 0.89 (0.24) 0.13 ...Missing; n (%) 56,570 (56.6%) 15,910 (58.1%) 92,700 (94.3%) 18,201 (96.2%) N/A N/A 149,270 (75.3%) 34,111 (73.7%) 0.04

Lab result number- HDL level (mg/dl) mean (only =<5000 included) v2 36,599 9,688 5,805 994 N/A N/A 42,404 10,682 ...mean (sd) 45.86 (13.58) 44.26 (12.89) 44.94 (13.83) 47.81 (132.54) N/A N/A 45.73 (13.61) 44.59 (42.24) 0.04 ...median [IQR] 44.00 [37.00, 53.00] 42.00 [36.00, 51.00] 43.00 [36.00, 52.00] 42.00 [35.00, 50.00] N/A N/A 43.86 (13.61) 42.00 (42.24) 0.06 ...Missing; n (%) 63,304 (63.4%) 17,706 (64.6%) 92,540 (94.1%) 17,918 (94.7%) N/A N/A 155,844 (78.6%) 35,624 (76.9%) 0.04

Lab result number- LDL level (mg/dl) mean (only =<5000 included) v2 36,994 9,856 5,343 919 N/A N/A 42,337 10,775 ...mean (sd) 85.89 (39.91) 81.77 (40.57) 90.89 (42.17) 84.41 (40.86) N/A N/A 86.52 (40.20) 82.00 (40.60) 0.11 ...median [IQR] 83.50 [62.00, 108.75] 80.50 [58.00, 105.00] 89.00 [67.00, 116.00] 84.00 [61.00, 109.00] N/A N/A 84.19 (40.20) 80.80 (40.60) 0.08 ...Missing; n (%) 62,909 (63.0%) 17,538 (64.0%) 93,002 (94.6%) 17,993 (95.1%) N/A N/A 155,911 (78.6%) 35,531 (76.7%) 0.05

Lab result number- Total cholesterol (mg/dl) mean (only =<5000 included) v2 37,141 9,912 5,841 1,005 N/A N/A 42,982 10,917 ...mean (sd) 173.84 (47.32) 170.49 (47.05) 179.36 (49.26) 171.92 (49.48) N/A N/A 174.59 (47.59) 170.62 (47.28) 0.08 ...median [IQR] 167.50 [143.00, 198.00] 165.00 [139.00, 195.00] 174.00 [148.00, 205.00] 165.50 [140.25, 196.00] N/A N/A 168.38 (47.59) 165.05 (47.28) 0.07 ...Missing; n (%) 62,762 (62.8%) 17,482 (63.8%) 92,504 (94.1%) 17,907 (94.7%) N/A N/A 155,266 (78.3%) 35,389 (76.4%) 0.05

Lab result number- Triglyceride level (mg/dl) mean (only =<5000 included) v2 36,825 9,846 5,753 987 N/A N/A 42,578 10,833 ...mean (sd) 193.49 (177.23) 207.63 (200.82) 197.08 (184.91) 210.43 (212.46) N/A N/A 193.98 (178.29) 207.89 (201.92) -0.07 ...median [IQR] 155.00 [110.00, 223.00] 160.00 [113.00, 236.00] 153.00 [106.50, 228.25] 157.50 [109.00, 233.00] N/A N/A 154.73 (178.29) 159.77 (201.92) -0.03 ...Missing; n (%) 63,078 (63.1%) 17,548 (64.1%) 92,592 (94.2%) 17,925 (94.8%) N/A N/A 155,670 (78.5%) 35,473 (76.6%) 0.05

Lab result number- Hemoglobin mean (only >0 included) 28,791 7,333 4,328 643 N/A N/A 33,119 7,976 ...mean (sd) 13.72 (1.56) 14.15 (1.49) 6,342.54 (215,464.58) 1,919.68 (16,045.24) N/A N/A 840.77 (77884.39) 167.77 (4553.05) 0.01 ...median [IQR] 13.70 [12.65, 14.80] 14.10 [13.10, 15.20] 13.90 [12.85, 15.00] 14.00 [13.00, 15.00] N/A N/A #VALUE! #VALUE! #VALUE! ...Missing; n (%) 71,112 (71.2%) 20,061 (73.2%) 94,017 (95.6%) 18,269 (96.6%) N/A N/A 165,129 (83.3%) 38,330 (82.8%) 0.01

Lab result number- Serum sodium mean (only > 90 and < 190 included) 42,353 11,249 6,243 1,027 N/A N/A 48,596 12,276 ...mean (sd) 139.42 (2.77) 139.45 (2.68) 138.82 (2.61) 139.17 (2.53) N/A N/A 139.34 (2.75) 139.43 (2.67) -0.03 ...median [IQR] 139.50 [138.00, 141.00] 139.50 [138.00, 141.00] 139.00 [137.00, 140.50] 139.00 [137.50, 141.00] N/A N/A 139.44 (2.75) 139.46 (2.67) -0.01 ...Missing; n (%) 57,550 (57.6%) 16,145 (58.9%) 92,102 (93.7%) 17,885 (94.6%) N/A N/A 149,652 (75.5%) 34,030 (73.5%) 0.05

Lab result number- Albumin mean (only >0 and <=10 included) 39,793 10,600 5,330 848 N/A N/A 45,123 11,448 ...mean (sd) 4.29 (0.32) 4.32 (0.31) 4.20 (0.38) 4.10 (0.39) N/A N/A 4.28 (0.33) 4.30 (0.32) -0.06 ...median [IQR] 4.30 [4.10, 4.50] 4.30 [4.10, 4.50] 4.20 [4.00, 4.45] 4.00 [4.00, 4.30] N/A N/A 4.29 (0.33) 4.28 (0.32) 0.03 ...Missing; n (%) 60,110 (60.2%) 16,794 (61.3%) 93,015 (94.6%) 18,064 (95.5%) N/A N/A 153,125 (77.2%) 34,858 (75.3%) 0.04

Lab result number- Glucose (fasting or random) mean (only 10-1000 included) 42,469 11,283 6,343 1,054 N/A N/A 48,812 12,337 ...mean (sd) 178.34 (72.25) 182.55 (71.67) 181.56 (74.01) 177.65 (69.16) N/A N/A 178.76 (72.48) 182.13 (71.46) -0.05 ...median [IQR] 161.00 [129.00, 209.50] 167.00 [132.50, 217.00] 163.00 [130.50, 215.50] 161.75 [129.00, 209.00] N/A N/A 161.26 (72.48) 166.55 (71.46) -0.07 ...Missing; n (%) 57,434 (57.5%) 16,111 (58.8%) 92,002 (93.6%) 17,858 (94.4%) N/A N/A 149,436 (75.4%) 33,969 (73.4%) 0.05

Lab result number- Potassium mean (only 1-7 included) 43,384 11,485 6,118 973 N/A N/A 49,502 12,458 ...mean (sd) 4.48 (0.43) 4.47 (0.40) 4.32 (0.46) 4.16 (0.50) N/A N/A 4.46 (0.43) 4.45 (0.41) 0.02 ...median [IQR] 4.50 [4.20, 4.70] 4.45 [4.20, 4.70] 4.30 [4.00, 4.60] 4.00 [4.00, 4.50] N/A N/A 4.48 (0.43) 4.41 (0.41) 0.17 ...Missing; n (%) 56,519 (56.6%) 15,909 (58.1%) 92,227 (93.8%) 17,939 (94.9%) N/A N/A 148,746 (75.0%) 33,848 (73.1%) 0.04 Comorbidity Scores CCI (180 days)- ICD9 and ICD10 v2 ...mean (sd) 2.43 (1.80) 2.25 (1.47) 1.64 (1.30) 1.67 (1.06) 2.63 (1.89) 2.46 (1.56) 2.34 (1.74) 2.11 (1.38) 0.15 ...median [IQR] 2.00 [1.00, 3.00] 2.00 [1.00, 3.00] 1.00 [1.00, 2.00] 2.00 [1.00, 2.00] 2.00 [1.00, 4.00] 2.00 [1.00, 3.00] 1.76 (1.74) 2.00 (1.38) -0.15

Frailty Score: Qualitative Version 365 days as Categories, v1 ...0; n (%) 68,126 (68.2%) 23,602 (86.2%) 60,170 (61.2%) 14,653 (77.5%) 92,074 (45.3%) 10,006 (76.1%) 220,370 (54.9%) 48,261 (81.2%) -0.59 ...1 to 2; n (%) 24,208 (24.2%) 3,375 (12.3%) 29,743 (30.2%) 3,605 (19.1%) 66,971 (32.9%) 2,319 (17.6%) 120,922 (30.1%) 9,299 (15.6%) 0.35 ...3 or more; n (%) 7,569 (7.6%) 417 (1.5%) 8,432 (8.6%) 654 (3.5%) 44,249 (21.8%) 831 (6.3%) 60,250 (15.0%) 1,902 (3.2%) 0.42

Frailty Score: Empirical Version 365 days as Categories, v3 ...< 0.12908; n (%) 28,978 (29.0%) 9,111 (33.3%) 32,840 (33.4%) 6,951 (36.8%) 26,735 (13.2%) 2,162 (16.4%) 88,553 (22.1%) 18,224 (30.6%) -0.19 ...0.12908 - 0.1631167; n (%) 33,399 (33.4%) 9,641 (35.2%) 36,156 (36.8%) 7,300 (38.6%) 55,651 (27.4%) 4,179 (31.8%) 125,206 (31.2%) 21,120 (35.5%) -0.09 ...>= 0.1631167; n (%) 37,526 (37.6%) 8,642 (31.5%) 29,349 (29.8%) 4,661 (24.6%) 120,908 (59.5%) 6,815 (51.8%) 187,783 (46.8%) 20,118 (33.8%) 0.27 Non-Frailty; n (%) 57,586 (57.6%) 16,315 (59.6%) 50,767 (51.6%) 10,157 (53.7%) 10,528 (5.2%) 611 (4.6%) 118,881 (29.6%) 27,083 (45.5%) -0.33

Frailty Score (mean): Qualitative Version 365 days, v1 ...mean (sd) 0.64 (1.29) 0.21 (0.64) 0.75 (1.28) 0.37 (0.86) 1.43 (1.93) 0.48 (1.11) 1.07 (1.64) 0.32 (0.83) 0.58 ...median [IQR] 0.00 [0.00, 1.00] 0.00 [0.00, 0.00] 0.00 [0.00, 1.00] 0.00 [0.00, 0.00] 1.00 [0.00, 2.00] 0.00 [0.00, 0.00] 0.51 (1.64) 0.00 (0.83) 0.39 Frailty Score (mean): Empirical Version 365 days, v2 ...mean (sd) 0.16 (0.05) 0.15 (0.04) 0.15 (0.04) 0.14 (0.03) 0.19 (0.06) 0.17 (0.05) 0.17 (0.05) 0.15 (0.04) 0.44 ...median [IQR] 0.15 [0.13, 0.18] 0.14 [0.12, 0.17] 0.14 [0.12, 0.16] 0.13 [0.12, 0.16] 0.17 [0.14, 0.22] 0.17 [0.14, 0.20] 0.16 (0.05) 0.14 (0.04) 0.44 Healthcare Utilization Any hospitalization; n (%) 5,497 (5.5%) 1,088 (4.0%) 3,358 (3.4%) 417 (2.2%) 12,442 (6.1%) 482 (3.7%) 21,297 (5.3%) 1,987 (3.3%) 0.10 Any hospitalization within prior 30 days; n (%) 1,947 (1.9%) 275 (1.0%) 982 (1.0%) 61 (0.3%) 3,634 (1.8%) 65 (0.5%) 6,563 (1.6%) 401 (0.7%) 0.08 Any hospitalization during prior 31-180 days; n (%) 3,821 (3.8%) 845 (3.1%) 2,452 (2.5%) 362 (1.9%) 9,387 (4.6%) 424 (3.2%) 15,660 (3.9%) 1,631 (2.7%) 0.07 Endocrinologist Visit; n (%) 9,696 (9.7%) 6,083 (22.2%) 8,916 (9.1%) 4,696 (24.8%) 24,295 (12.0%) 3,503 (26.6%) 42,907 (10.7%) 14,282 (24.0%) -0.36 Endocrinologist Visit (30 days prior); n (%) 6,358 (6.4%) 4,656 (17.0%) 5,990 (6.1%) 3,590 (19.0%) 15,500 (7.6%) 2,720 (20.7%) 27,848 (6.9%) 10,966 (18.4%) -0.35 Endocrinologist Visit (31 to 180 days prior); n (%) 6,561 (6.6%) 4,086 (14.9%) 5,999 (6.1%) 3,222 (17.0%) 17,451 (8.6%) 2,594 (19.7%) 30,011 (7.5%) 9,902 (16.7%) -0.28 Internal medicine/family medicine visits; n (%) 79,699 (79.8%) 19,568 (71.4%) 85,692 (87.1%) 15,991 (84.6%) 164,752 (81.0%) 10,436 (79.3%) 330,143 (82.2%) 45,995 (77.4%) 0.12

Internal medicine/family medicine visits (30 days prior) v2; n (%) 59,806 (59.9%) 14,110 (51.5%) 64,158 (65.2%) 11,352 (60.0%) 116,541 (57.3%) 7,146 (54.3%) 240,505 (59.9%) 32,608 (54.8%) 0.10

Internal medicine/family medicine visits (31 to 180 days prior) v2; n (%)68,510 (68.6%) 16,887 (61.6%) 69,171 (70.3%) 13,393 (70.8%) 142,940 (70.3%) 9,188 (69.8%) 280,621 (69.9%) 39,468 (66.4%) 0.08 Cardiologist visit; n (%) 23,368 (23.4%) 6,777 (24.7%) 14,980 (15.2%) 3,006 (15.9%) 60,430 (29.7%) 4,227 (32.1%) 98,778 (24.6%) 14,010 (23.6%) 0.02 Number of Cardiologist visits (30 days prior); n (%) 8,018 (8.0%) 2,440 (8.9%) 4,841 (4.9%) 894 (4.7%) 19,046 (9.4%) 1,399 (10.6%) 31,905 (7.9%) 4,733 (8.0%) 0.00

Number of Cardiologist visits (31 to 180 days prior); n (%) 19,586 (19.6%) 5,663 (20.7%) 12,542 (12.8%) 2,550 (13.5%) 52,580 (25.9%) 3,650 (27.7%) 84,708 (21.1%) 11,863 (20.0%) 0.03 Electrocardiogram v2; n (%) 26,602 (26.6%) 7,163 (26.1%) 22,603 (23.0%) 4,033 (21.3%) 61,061 (30.0%) 4,106 (31.2%) 110,266 (27.5%) 15,302 (25.7%) 0.04 Use of glucose test strips; n (%) 3,648 (3.7%) 852 (3.1%) 3,332 (3.4%) 754 (4.0%) 6,468 (3.2%) 414 (3.1%) 13,448 (3.3%) 2,020 (3.4%) -0.01 Dialysis; n (%) 26 (0.0%) 1 (0.0%) 10 (0.0%) 0 (0.0%) 108 (0.1%) 1 (0.0%) 144 (0.0%) 002 (0.0%) #DIV/0! Naive new user v8 Copy; n (%) 13,650 (13.7%) 1,877 (6.9%) 13,152 (13.4%) 1,106 (5.8%) 24,032 (11.8%) 647 (4.9%) 50,834 (12.7%) 3,630 (6.1%) 0.23 N antidiabetic drugs at index date v3 Copy ...mean (sd) 2.26 (0.83) 2.34 (0.93) 2.28 (0.82) 2.39 (0.96) 2.23 (0.83) 2.44 (0.93) 2.25 (0.83) 2.38 (0.94) -0.15 ...median [IQR] 2.00 [2.00, 3.00] 2.00 [2.00, 3.00] 2.00 [2.00, 3.00] 2.00 [2.00, 3.00] 2.00 [2.00, 3.00] 2.00 [2.00, 3.00] 2.00 (0.83) 2.00 (0.94) 0.00 number of different/distinct medication prescriptions ...mean (sd) 9.99 (4.61) 10.50 (4.73) 8.93 (4.09) 9.97 (4.24) 9.91 (4.25) 10.60 (4.22) 9.69 (4.30) 10.35 (4.47) -0.15 ...median [IQR] 9.00 [7.00, 12.00] 10.00 [7.00, 13.00] 8.00 [6.00, 11.00] 9.00 [7.00, 12.00] 9.00 [7.00, 12.00]10.00 [8.00, 13.00] 8.76 (4.30) 9.68 (4.47) -0.21 Number of Hospitalizations ...mean (sd) 0.07 (0.30) 0.05 (0.24) 0.04 (0.21) 0.02 (0.16) 0.07 (0.32) 0.04 (0.23) 0.06 (0.29) 0.04 (0.22) 0.08 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 (0.29) 0.00 (0.22) 0.00 Number of hospital days ...mean (sd) 0.37 (2.52) 0.21 (1.44) 0.19 (1.51) 0.10 (0.90) 0.45 (2.78) 0.19 (1.28) 0.37 (2.46) 0.17 (1.26) 0.10 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 (2.46) 0.00 (1.26) 0.00 Number of Emergency Department (ED) visits v3 ...mean (sd) 0.38 (1.19) 0.30 (1.09) 0.07 (0.75) 0.05 (0.57) 0.43 (1.21) 0.30 (0.93) 0.33 (1.11) 0.22 (0.92) 0.11 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 (1.11) 0.00 (0.92) 0.00 Number of Office visits ...mean (sd) 4.40 (3.47) 4.68 (3.48) 3.93 (3.12) 4.16 (3.11) 4.87 (3.70) 5.39 (3.66) 4.52 (3.51) 4.67 (3.41) -0.04 ...median [IQR] 4.00 [2.00, 6.00] 4.00 [2.00, 6.00] 3.00 [2.00, 5.00] 3.00 [2.00, 5.00] 4.00 [2.00, 7.00] 5.00 [3.00, 7.00] 3.76 (3.51) 3.90 (3.41) -0.04 Number of Endocrinologist visits ...mean (sd) 0.44 (2.07) 1.13 (3.39) 0.41 (2.05) 1.25 (3.46) 0.63 (2.84) 1.59 (4.88) 0.53 (2.49) 1.27 (3.79) -0.23 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 1.00] 0.00 (2.49) 0.00 (3.79) 0.00 Number of internal medicine/family medicine visits ...mean (sd) 8.66 (12.52) 7.06 (10.58) 6.43 (7.97) 6.12 (7.44) 6.99 (9.20) 6.58 (8.74) 7.27 (9.87) 6.65 (9.28) 0.06 ...median [IQR] 5.00 [1.00, 11.00] 4.00 [0.00, 9.00] 4.00 [2.00, 8.00] 4.00 [2.00, 8.00] 4.00 [1.00, 9.00] 4.00 [1.00, 9.00] 4.25 (9.87) 4.00 (9.28) 0.03 Number of Cardiologist visits ...mean (sd) 1.05 (3.12) 1.18 (3.46) 0.59 (2.18) 0.60 (2.16) 1.39 (3.76) 1.50 (3.89) 1.11 (3.28) 1.07 (3.22) 0.01 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 1.00] 0.00 [0.00, 1.00] 0.00 (3.28) 0.00 (3.22) 0.00 Number electrocardiograms received v2 ...mean (sd) 0.49 (1.20) 0.47 (1.16) 0.37 (0.88) 0.33 (0.83) 0.56 (1.18) 0.55 (1.12) 0.50 (1.12) 0.44 (1.06) 0.06 ...median [IQR] 0.00 [0.00, 1.00] 0.00 [0.00, 1.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 1.00] 0.00 [0.00, 1.00] 0.00 (1.12) 0.00 (1.06) 0.00 Number of HbA1c tests ordered ...mean (sd) 1.29 (0.88) 1.37 (0.88) 1.09 (0.85) 1.33 (0.82) 1.41 (0.85) 1.57 (0.81) 1.30 (0.86) 1.40 (0.85) -0.12 ...median [IQR] 1.00 [1.00, 2.00] 1.00 [1.00, 2.00] 1.00 [0.00, 2.00] 1.00 [1.00, 2.00] 1.00 [1.00, 2.00] 2.00 [1.00, 2.00] 1.00 (0.86) 1.22 (0.85) -0.26 Number of glucose tests ordered ...mean (sd) 0.55 (3.54) 0.46 (1.58) 0.34 (1.10) 0.43 (1.22) 0.42 (1.02) 0.48 (1.08) 0.43 (1.99) 0.45 (1.37) -0.01 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 1.00] 0.00 (1.99) 0.00 (1.37) 0.00 Number of lipid tests ordered ...mean (sd) 0.97 (0.91) 1.01 (0.94) 0.89 (1.17) 1.05 (1.16) 0.98 (0.81) 1.07 (0.83) 0.96 (0.93) 1.04 (0.99) -0.08 ...median [IQR] 1.00 [0.00, 1.00] 1.00 [0.00, 1.00] 1.00 [0.00, 1.00] 1.00 [0.00, 1.00] 1.00 [0.00, 1.00] 1.00 [1.00, 2.00] 1.00 (0.93) 1.00 (0.99) 0.00 Number of creatinine tests ordered ...mean (sd) 0.04 (0.26) 0.04 (0.25) 0.03 (0.23) 0.04 (0.25) 0.06 (0.32) 0.07 (0.34) 0.05 (0.29) 0.05 (0.27) 0.00 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 (0.29) 0.00 (0.27) 0.00 Number of BUN tests ordered ...mean (sd) 0.02 (0.20) 0.02 (0.17) 0.02 (0.18) 0.02 (0.17) 0.04 (0.26) 0.04 (0.26) 0.03 (0.23) 0.02 (0.19) 0.05 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 (0.23) 0.00 (0.19) 0.00 Number of tests for microalbuminuria ...mean (sd) 0.81 (1.17) 0.87 (1.18) 0.64 (1.03) 0.81 (1.12) 0.48 (0.70) 0.56 (0.71) 0.60 (0.92) 0.78 (1.07) -0.18 ...median [IQR] 0.00 [0.00, 2.00] 0.00 [0.00, 2.00] 0.00 [0.00, 1.00] 0.00 [0.00, 2.00] 0.00 [0.00, 1.00] 0.00 [0.00, 1.00] 0.00 (0.92) 0.00 (1.07) 0.00

Total N distinct ICD9/ICD10 diagnoses at the 3rd digit level Copy ...mean (sd) 6.92 (7.38) 8.25 (6.87) 2.91 (3.94) 3.91 (3.75) 6.39 (7.39) 8.79 (7.04) 5.67 (6.71) 6.99 (6.10) -0.21 ...median [IQR] 5.00 [0.00, 10.00] 7.00 [4.00, 11.00] 2.00 [0.00, 5.00] 4.00 [0.00, 6.00] 5.00 [0.00, 10.00] 7.00 [4.00, 12.00] 4.27 (6.71) 6.05 (6.10) -0.28

Use of thiazide; n (%) 11,963 (12.0%) 3,080 (11.2%) 10,371 (10.5%) 1,926 (10.2%) 27,843 (13.7%) 1,804 (13.7%) 50,177 (12.5%) 6,810 (11.5%) 0.03 Use of beta blockers; n (%) 36,576 (36.6%) 9,851 (36.0%) 30,224 (30.7%) 5,661 (29.9%) 96,233 (47.3%) 6,419 (48.8%) 163,033 (40.6%) 21,931 (36.9%) 0.08 Use of calcium channel blockers; n (%) 30,078 (30.1%) 7,288 (26.6%) 26,215 (26.7%) 4,370 (23.1%) 69,690 (34.3%) 4,001 (30.4%) 125,983 (31.4%) 15,659 (26.3%) 0.11 PS-matched

Optum MarketScan Medicare POOLED Exposure - Empagliflozin Exposure - Empagliflozin Exposure - Empagliflozin Exposure - Empagliflozin Variable Reference- DPP4i v2 v3 Reference- DPP4i v2 v3 Reference- DPP4i v2 v3 Reference- DPP4i v2 v3 St. Diff. Number of patients 23348 23348 16256 16256 12272 12272 51,876 51,876 Age ...mean (sd) 61.08 (11.75) 61.21 (10.55) 55.44 (10.20) 55.68 (8.79) 71.62 (5.53) 71.60 (5.25) 61.81 (10.10) 61.94 (8.99) -0.01 ...median [IQR] 62.00 [53.00, 70.00] 62.00 [54.00, 69.00] 56.00 [49.00, 62.00] 56.00 [50.00, 61.00] 70.00 [67.00, 75.00] 70.00 [68.00, 74.00] 62.01 (10.10) 62.01 (8.99) 0.00 Age categories without zero category ...18 - 54; n (%) 6,768 (29.0%) 6,110 (26.2%) 7,240 (44.5%) 6,673 (41.0%) 0 (0.0%) 0 (0.0%) 14,008 (27.0%) 12,783 (24.6%) 0.05 ...55 - 64; n (%) 6,221 (26.6%) 7,436 (31.8%) 6,822 (42.0%) 7,932 (48.8%) 52 (0.4%) 40 (0.3%) 13,095 (25.2%) 15,408 (29.7%) -0.10 ...65 - 74; n (%) 7,676 (32.9%) 7,642 (32.7%) 1,550 (9.5%) 1,304 (8.0%) 9,051 (73.8%) 9,197 (74.9%) 18,277 (35.2%) 18,143 (35.0%) 0.00 ...>= 75; n (%) 2,683 (11.5%) 2,160 (9.3%) 644 (4.0%) 347 (2.1%) 3,169 (25.8%) 3,035 (24.7%) 6,496 (12.5%) 5,542 (10.7%) 0.06 Gender without zero category- United ...Males; n (%) 13,845 (59.3%) 13,961 (59.8%) 10,178 (62.6%) 10,081 (62.0%) 6,728 (54.8%) 6,895 (56.2%) 30,751 (59.3%) 30,937 (59.6%) -0.01 ...Females; n (%) 9,503 (40.7%) 9,387 (40.2%) 6,078 (37.4%) 6,175 (38.0%) 5,544 (45.2%) 5,377 (43.8%) 21,125 (40.7%) 20,939 (40.4%) 0.01 Race ...White; n (%) N/A N/A N/A N/A 10,037 (81.8%) 10,017 (81.6%) 10,037 (81.8%) 10,017 (81.6%) 0.01 ...Black; n (%) N/A N/A N/A N/A 888 (7.2%) 888 (7.2%) 888 (7.2%) 888 (7.2%) 0.00 ...Asian; n (%) N/A N/A N/A N/A 390 (3.2%) 380 (3.1%) 390 (3.2%) 380 (3.1%) 0.01 ...Hispanic; n (%) N/A N/A N/A N/A 311 (2.5%) 323 (2.6%) 311 (2.5%) 323 (2.6%) -0.01 ...North American Native; n (%) N/A N/A N/A N/A 45 (0.4%) 57 (0.5%) 45 (0.4%) 57 (0.5%) -0.01 ...Other/Unknown; n (%) N/A N/A N/A N/A 601 (4.9%) 607 (4.9%) 601 (4.9%) 607 (4.9%) 0.00 Region without zero category- United v3 (lumping missing&other category with West) ...Northeast; n (%) 2,022 (8.7%) 2,021 (8.7%) 2,167 (13.3%) 2,230 (13.7%) 2,343 (19.1%) 2,302 (18.8%) 6,532 (12.6%) 6,553 (12.6%) 0.00 ...South; n (%) 13,003 (55.7%) 12,998 (55.7%) 2,850 (17.5%) 2,885 (17.7%) 5,178 (42.2%) 5,190 (42.3%) 21,031 (40.5%) 21,073 (40.6%) 0.00 ...Midwest; n (%) 4,586 (19.6%) 4,543 (19.5%) 9,493 (58.4%) 9,421 (58.0%) 2,316 (18.9%) 2,365 (19.3%) 16,395 (31.6%) 16,329 (31.5%) 0.00 ...West; n (%) 3,737 (16.0%) 3,786 (16.2%) 1,691 (10.4%) 1,668 (10.3%) 2,435 (19.8%) 2,415 (19.7%) 7,863 (15.2%) 7,869 (15.2%) 0.00 ...Unknown+missing; n (%) N/A N/A 55 (0.3%) 52 (0.3%) N/A N/A 55 (0.3%) 52 (0.3%) 0.00 CV Covariates Ischemic heart disease; n (%) 4,687 (20.1%) 4,837 (20.7%) 2,107 (13.0%) 2,129 (13.1%) 3,827 (31.2%) 3,854 (31.4%) 10,621 (20.5%) 10,820 (20.9%) -0.01 Acute MI; n (%) 239 (1.0%) 262 (1.1%) 71 (0.4%) 84 (0.5%) 90 (0.7%) 84 (0.7%) 400 (0.8%) 430 (0.8%) 0.00 ACS/unstable angina; n (%) 179 (0.8%) 193 (0.8%) 105 (0.6%) 92 (0.6%) 122 (1.0%) 108 (0.9%) 406 (0.8%) 393 (0.8%) 0.00 Old MI; n (%) 638 (2.7%) 674 (2.9%) 171 (1.1%) 158 (1.0%) 413 (3.4%) 422 (3.4%) 1,222 (2.4%) 1,254 (2.4%) 0.00 Stable angina; n (%) 897 (3.8%) 907 (3.9%) 327 (2.0%) 316 (1.9%) 545 (4.4%) 580 (4.7%) 1,769 (3.4%) 1,803 (3.5%) -0.01 Coronary atherosclerosis and other forms of chronic ischemic heart disease; n (%) 4,436 (19.0%) 4,547 (19.5%) 1,994 (12.3%) 2,015 (12.4%) 3,684 (30.0%) 3,737 (30.5%) 10,114 (19.5%) 10,299 (19.9%) -0.01 Other atherosclerosis with ICD10 v2 Copy; n (%) 89 (0.4%) 88 (0.4%) 42 (0.3%) 51 (0.3%) 88 (0.7%) 83 (0.7%) 219 (0.4%) 222 (0.4%) 0.00 Previous cardiac procedure (CABG or PTCA or Stent) v4; n (%) 130 (0.6%) 148 (0.6%) 43 (0.3%) 37 (0.2%) 44 (0.4%) 53 (0.4%) 217 (0.4%) 238 (0.5%) -0.01 History of CABG or PTCA; n (%) 1,241 (5.3%) 1,320 (5.7%) 286 (1.8%) 298 (1.8%) 1,032 (8.4%) 1,055 (8.6%) 2,559 (4.9%) 2,673 (5.2%) -0.01 Any stroke; n (%) 989 (4.2%) 992 (4.2%) 248 (1.5%) 233 (1.4%) 571 (4.7%) 549 (4.5%) 1,808 (3.5%) 1,774 (3.4%) 0.01 Ischemic stroke (w and w/o mention of cerebral infarction); n (%) 973 (4.2%) 983 (4.2%) 246 (1.5%) 232 (1.4%) 563 (4.6%) 544 (4.4%) 1,782 (3.4%) 1,759 (3.4%) 0.00 Hemorrhagic stroke; n (%) 29 (0.1%) 17 (0.1%) 7 (0.0%) 2 (0.0%) 10 (0.1%) 6 (0.0%) 046 (0.1%) 025 (0.0%) 0.04 TIA; n (%) 218 (0.9%) 240 (1.0%) 69 (0.4%) 64 (0.4%) 94 (0.8%) 94 (0.8%) 381 (0.7%) 398 (0.8%) -0.01 Other cerebrovascular disease; n (%) 286 (1.2%) 295 (1.3%) 84 (0.5%) 75 (0.5%) 231 (1.9%) 224 (1.8%) 601 (1.2%) 594 (1.1%) 0.01 Late effects of cerebrovascular disease; n (%) 197 (0.8%) 220 (0.9%) 34 (0.2%) 31 (0.2%) 99 (0.8%) 104 (0.8%) 330 (0.6%) 355 (0.7%) -0.01 Cerebrovascular procedure; n (%) 15 (0.1%) 25 (0.1%) 2 (0.0%) 3 (0.0%) 4 (0.0%) 7 (0.1%) 021 (0.0%) 035 (0.1%) -0.04 Heart failure (CHF); n (%) 1,198 (5.1%) 1,210 (5.2%) 345 (2.1%) 345 (2.1%) 908 (7.4%) 889 (7.2%) 2,451 (4.7%) 2,444 (4.7%) 0.00 Peripheral Vascular Disease (PVD) or PVD Surgery v2; n (%) 1,272 (5.4%) 1,262 (5.4%) 402 (2.5%) 418 (2.6%) 1,069 (8.7%) 1,110 (9.0%) 2,743 (5.3%) 2,790 (5.4%) 0.00 Atrial fibrillation; n (%) 1,122 (4.8%) 1,134 (4.9%) 404 (2.5%) 416 (2.6%) 1,119 (9.1%) 1,181 (9.6%) 2,645 (5.1%) 2,731 (5.3%) -0.01 Other cardiac dysrhythmia; n (%) 1,858 (8.0%) 1,828 (7.8%) 684 (4.2%) 686 (4.2%) 1,650 (13.4%) 1,687 (13.7%) 4,192 (8.1%) 4,201 (8.1%) 0.00 Cardiac conduction disorders; n (%) 478 (2.0%) 492 (2.1%) 155 (1.0%) 165 (1.0%) 436 (3.6%) 421 (3.4%) 1,069 (2.1%) 1,078 (2.1%) 0.00 Other CVD; n (%) 1,898 (8.1%) 1,910 (8.2%) 732 (4.5%) 706 (4.3%) 1,590 (13.0%) 1,562 (12.7%) 4,220 (8.1%) 4,178 (8.1%) 0.00 Diabetes-related complications Diabetic retinopathy; n (%) 1,700 (7.3%) 1,711 (7.3%) 583 (3.6%) 603 (3.7%) 1,180 (9.6%) 1,158 (9.4%) 3,463 (6.7%) 3,472 (6.7%) 0.00 Diabetes with other ophthalmic manifestations; n (%) 202 (0.9%) 200 (0.9%) 227 (1.4%) 263 (1.6%) 245 (2.0%) 251 (2.0%) 674 (1.3%) 714 (1.4%) -0.01 Retinal detachment, vitreous hemorrhage, vitrectomy; n (%) 108 (0.5%) 109 (0.5%) 56 (0.3%) 58 (0.4%) 62 (0.5%) 75 (0.6%) 226 (0.4%) 242 (0.5%) -0.01 Retinal laser coagulation therapy; n (%) 129 (0.6%) 128 (0.5%) 91 (0.6%) 97 (0.6%) 108 (0.9%) 67 (0.5%) 328 (0.6%) 292 (0.6%) 0.00 Occurrence of Diabetic Neuropathy v2 Copy; n (%) 4,694 (20.1%) 4,709 (20.2%) 2,034 (12.5%) 2,085 (12.8%) 2,947 (24.0%) 2,968 (24.2%) 9,675 (18.7%) 9,762 (18.8%) 0.00 Occurrence of diabetic nephropathy V3 with ICD10 Copy; n (%) 2,816 (12.1%) 2,800 (12.0%) 1,068 (6.6%) 1,075 (6.6%) 1,347 (11.0%) 1,376 (11.2%) 5,231 (10.1%) 5,251 (10.1%) 0.00 Hypoglycemia v2; n (%) 116 (0.5%) 132 (0.6%) 162 (1.0%) 166 (1.0%) 94 (0.8%) 100 (0.8%) 372 (0.7%) 398 (0.8%) -0.01 Hyperglycemia; n (%) 1,012 (4.3%) 979 (4.2%) 476 (2.9%) 468 (2.9%) 444 (3.6%) 443 (3.6%) 1,932 (3.7%) 1,890 (3.6%) 0.01 Disorders of fluid electrolyte and acid-base balance; n (%) 991 (4.2%) 988 (4.2%) 374 (2.3%) 378 (2.3%) 446 (3.6%) 454 (3.7%) 1,811 (3.5%) 1,820 (3.5%) 0.00 Diabetic ketoacidosis; n (%) 89 (0.4%) 65 (0.3%) 52 (0.3%) 37 (0.2%) 26 (0.2%) 22 (0.2%) 167 (0.3%) 124 (0.2%) 0.02 Hyperosmolar hyperglycemic nonketotic syndrome (HONK); n (%) 147 (0.6%) 142 (0.6%) 86 (0.5%) 81 (0.5%) 81 (0.7%) 71 (0.6%) 314 (0.6%) 294 (0.6%) 0.00 Diabetes with peripheral circulatory disorders with ICD-10 v2 Copy; n (%) 1,612 (6.9%) 1,591 (6.8%) 476 (2.9%) 496 (3.1%) 969 (7.9%) 1,028 (8.4%) 3,057 (5.9%) 3,115 (6.0%) 0.00 Diabetic Foot; n (%) 461 (2.0%) 472 (2.0%) 263 (1.6%) 257 (1.6%) 252 (2.1%) 256 (2.1%) 976 (1.9%) 985 (1.9%) 0.00 Gangrene v2; n (%) 61 (0.3%) 53 (0.2%) 25 (0.2%) 21 (0.1%) 25 (0.2%) 32 (0.3%) 111 (0.2%) 106 (0.2%) 0.00 Lower extremity amputation; n (%) 183 (0.8%) 171 (0.7%) 49 (0.3%) 54 (0.3%) 78 (0.6%) 72 (0.6%) 310 (0.6%) 297 (0.6%) 0.00 Osteomyelitis; n (%) 118 (0.5%) 126 (0.5%) 66 (0.4%) 61 (0.4%) 52 (0.4%) 46 (0.4%) 236 (0.5%) 233 (0.4%) 0.01 Skin infections v2; n (%) 1,105 (4.7%) 1,155 (4.9%) 695 (4.3%) 736 (4.5%) 713 (5.8%) 721 (5.9%) 2,513 (4.8%) 2,612 (5.0%) -0.01 Erectile dysfunction; n (%) 919 (3.9%) 952 (4.1%) 524 (3.2%) 498 (3.1%) 423 (3.4%) 438 (3.6%) 1,866 (3.6%) 1,888 (3.6%) 0.00 Diabetes with unspecified complication; n (%) 1,546 (6.6%) 1,562 (6.7%) 1,045 (6.4%) 1,063 (6.5%) 833 (6.8%) 876 (7.1%) 3,424 (6.6%) 3,501 (6.7%) 0.00 Diabetes mellitus without mention of complications; n (%) 18,342 (78.6%) 18,336 (78.5%) 13,356 (82.2%) 13,330 (82.0%) 10,389 (84.7%) 10,422 (84.9%) 42,087 (81.1%) 42,088 (81.1%) 0.00 Hypertension: 1 inpatient or 2 outpatient claims within 365 days; n (%) 19,756 (84.6%) 19,798 (84.8%) 12,591 (77.5%) 12,543 (77.2%) 11,168 (91.0%) 11,166 (91.0%) 43,515 (83.9%) 43,507 (83.9%) 0.00 Hyperlipidemia v2; n (%) 16,347 (70.0%) 16,475 (70.6%) 11,408 (70.2%) 11,441 (70.4%) 9,390 (76.5%) 9,430 (76.8%) 37,145 (71.6%) 37,346 (72.0%) -0.01 Edema; n (%) 1,003 (4.3%) 1,042 (4.5%) 384 (2.4%) 401 (2.5%) 841 (6.9%) 828 (6.7%) 2,228 (4.3%) 2,271 (4.4%) 0.00 Renal Dysfunction (non-diabetic) v2; n (%) 2,892 (12.4%) 2,866 (12.3%) 837 (5.1%) 859 (5.3%) 1,770 (14.4%) 1,732 (14.1%) 5,499 (10.6%) 5,457 (10.5%) 0.00 Occurrence of acute renal disease v2; n (%) 309 (1.3%) 305 (1.3%) 63 (0.4%) 76 (0.5%) 131 (1.1%) 128 (1.0%) 503 (1.0%) 509 (1.0%) 0.00 Occurrence of chronic renal insufficiency; n (%) 2,117 (9.1%) 2,153 (9.2%) 588 (3.6%) 595 (3.7%) 1,397 (11.4%) 1,384 (11.3%) 4,102 (7.9%) 4,132 (8.0%) 0.00 Chronic kidney disease v2; n (%) 2,061 (8.8%) 2,076 (8.9%) 545 (3.4%) 556 (3.4%) 1,350 (11.0%) 1,322 (10.8%) 3,956 (7.6%) 3,954 (7.6%) 0.00 CKD Stage 3-4; n (%) 1,155 (4.9%) 1,169 (5.0%) 273 (1.7%) 283 (1.7%) 811 (6.6%) 802 (6.5%) 2,239 (4.3%) 2,254 (4.3%) 0.00 Occurrence of hypertensive nephropathy; n (%) 898 (3.8%) 888 (3.8%) 203 (1.2%) 201 (1.2%) 515 (4.2%) 507 (4.1%) 1,616 (3.1%) 1,596 (3.1%) 0.00 Occurrence of miscellaneous renal insufficiency v2; n (%) 764 (3.3%) 769 (3.3%) 240 (1.5%) 244 (1.5%) 527 (4.3%) 500 (4.1%) 1,531 (3.0%) 1,513 (2.9%) 0.01 Glaucoma or cataracts v2; n (%) 3,871 (16.6%) 3,796 (16.3%) 1,952 (12.0%) 1,917 (11.8%) 3,348 (27.3%) 3,361 (27.4%) 9,171 (17.7%) 9,074 (17.5%) 0.01 Cellulitis or abscess of toe; n (%) 287 (1.2%) 319 (1.4%) 151 (0.9%) 179 (1.1%) 171 (1.4%) 215 (1.8%) 609 (1.2%) 713 (1.4%) -0.02 Foot ulcer; n (%) 428 (1.8%) 426 (1.8%) 246 (1.5%) 236 (1.5%) 240 (2.0%) 242 (2.0%) 914 (1.8%) 904 (1.7%) 0.01 Bladder stones; n (%) 21 (0.1%) 23 (0.1%) 13 (0.1%) 10 (0.1%) 22 (0.2%) 17 (0.1%) 056 (0.1%) 050 (0.1%) 0.00 Kidney stones; n (%) 445 (1.9%) 451 (1.9%) 271 (1.7%) 250 (1.5%) 307 (2.5%) 274 (2.2%) 1,023 (2.0%) 975 (1.9%) 0.01 Urinary tract infections (UTIs); n (%) 1,193 (5.1%) 1,212 (5.2%) 528 (3.2%) 504 (3.1%) 874 (7.1%) 851 (6.9%) 2,595 (5.0%) 2,567 (4.9%) 0.00 Dipstick urinalysis; n (%) 7,565 (32.4%) 7,176 (30.7%) 4,919 (30.3%) 4,547 (28.0%) 4,298 (35.0%) 4,205 (34.3%) 16,782 (32.4%) 15,928 (30.7%) 0.04 Non-dipstick urinalysis; n (%) 10,468 (44.8%) 10,612 (45.5%) 7,062 (43.4%) 7,060 (43.4%) 5,815 (47.4%) 5,798 (47.2%) 23,345 (45.0%) 23,470 (45.2%) 0.00 Urine function test; n (%) 410 (1.8%) 347 (1.5%) 227 (1.4%) 173 (1.1%) 418 (3.4%) 394 (3.2%) 1,055 (2.0%) 914 (1.8%) 0.01 Cytology; n (%) 101 (0.4%) 102 (0.4%) 71 (0.4%) 49 (0.3%) 98 (0.8%) 59 (0.5%) 270 (0.5%) 210 (0.4%) 0.01 Cystoscopy; n (%) 164 (0.7%) 174 (0.7%) 106 (0.7%) 87 (0.5%) 146 (1.2%) 116 (0.9%) 416 (0.8%) 377 (0.7%) 0.01 Other Covariates Liver disease; n (%) 1,136 (4.9%) 1,109 (4.7%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1,136 (2.2%) 1,109 (2.1%) 0.01 Osteoarthritis; n (%) 3,067 (13.1%) 3,011 (12.9%) 1,288 (7.9%) 1,262 (7.8%) 2,374 (19.3%) 2,353 (19.2%) 6,729 (13.0%) 6,626 (12.8%) 0.01 Other arthritis, arthropathies and musculoskeletal pain; n (%) 7,431 (31.8%) 7,325 (31.4%) 4,197 (25.8%) 4,181 (25.7%) 4,601 (37.5%) 4,620 (37.6%) 16,229 (31.3%) 16,126 (31.1%) 0.00 Dorsopathies; n (%) 4,865 (20.8%) 4,905 (21.0%) 2,616 (16.1%) 2,650 (16.3%) 2,938 (23.9%) 2,977 (24.3%) 10,419 (20.1%) 10,532 (20.3%) 0.00 Fractures; n (%) 464 (2.0%) 423 (1.8%) 224 (1.4%) 242 (1.5%) 333 (2.7%) 319 (2.6%) 1,021 (2.0%) 984 (1.9%) 0.01 Falls v2; n (%) 479 (2.1%) 476 (2.0%) 103 (0.6%) 112 (0.7%) 324 (2.6%) 325 (2.6%) 906 (1.7%) 913 (1.8%) -0.01 Osteoporosis; n (%) 600 (2.6%) 591 (2.5%) 127 (0.8%) 135 (0.8%) 629 (5.1%) 607 (4.9%) 1,356 (2.6%) 1,333 (2.6%) 0.00 Hyperthyroidism; n (%) 141 (0.6%) 144 (0.6%) 95 (0.6%) 76 (0.5%) 118 (1.0%) 92 (0.7%) 354 (0.7%) 312 (0.6%) 0.01 Hypothyroidism v2; n (%) 2,998 (12.8%) 2,980 (12.8%) 1,888 (11.6%) 1,816 (11.2%) 842 (6.9%) 870 (7.1%) 5,728 (11.0%) 5,666 (10.9%) 0.00 Other disorders of thyroid gland V2; n (%) 918 (3.9%) 942 (4.0%) 608 (3.7%) 703 (4.3%) 602 (4.9%) 593 (4.8%) 2,128 (4.1%) 2,238 (4.3%) -0.01 Depression; n (%) 1,487 (6.4%) 1,529 (6.5%) 800 (4.9%) 783 (4.8%) 864 (7.0%) 858 (7.0%) 3,151 (6.1%) 3,170 (6.1%) 0.00 Anxiety; n (%) 2,025 (8.7%) 2,017 (8.6%) 951 (5.9%) 951 (5.9%) 971 (7.9%) 936 (7.6%) 3,947 (7.6%) 3,904 (7.5%) 0.00 Sleep_Disorder; n (%) 574 (2.5%) 597 (2.6%) 697 (4.3%) 689 (4.2%) 391 (3.2%) 401 (3.3%) 1,662 (3.2%) 1,687 (3.3%) -0.01 Dementia; n (%) 336 (1.4%) 350 (1.5%) 93 (0.6%) 86 (0.5%) 365 (3.0%) 353 (2.9%) 794 (1.5%) 789 (1.5%) 0.00 Delirium; n (%) 107 (0.5%) 101 (0.4%) 26 (0.2%) 27 (0.2%) 77 (0.6%) 77 (0.6%) 210 (0.4%) 205 (0.4%) 0.00 Psychosis; n (%) 171 (0.7%) 156 (0.7%) 24 (0.1%) 32 (0.2%) 61 (0.5%) 64 (0.5%) 256 (0.5%) 252 (0.5%) 0.00 Obesity; n (%) 6,100 (26.1%) 6,089 (26.1%) 1,385 (8.5%) 1,362 (8.4%) 719 (5.9%) 740 (6.0%) 8,204 (15.8%) 8,191 (15.8%) 0.00 Overweight; n (%) 1,909 (8.2%) 1,826 (7.8%) 615 (3.8%) 599 (3.7%) 595 (4.8%) 609 (5.0%) 3,119 (6.0%) 3,034 (5.8%) 0.01 Smoking; n (%) 2,775 (11.9%) 2,756 (11.8%) 809 (5.0%) 776 (4.8%) 1,294 (10.5%) 1,337 (10.9%) 4,878 (9.4%) 4,869 (9.4%) 0.00 Alcohol abuse or dependence; n (%) 204 (0.9%) 178 (0.8%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 204 (0.4%) 178 (0.3%) 0.02 Drug abuse or dependence; n (%) 335 (1.4%) 314 (1.3%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 335 (0.6%) 314 (0.6%) 0.00 COPD; n (%) 1,350 (5.8%) 1,322 (5.7%) 352 (2.2%) 347 (2.1%) 846 (6.9%) 854 (7.0%) 2,548 (4.9%) 2,523 (4.9%) 0.00 Asthma; n (%) 1,060 (4.5%) 1,048 (4.5%) 568 (3.5%) 514 (3.2%) 630 (5.1%) 601 (4.9%) 2,258 (4.4%) 2,163 (4.2%) 0.01 Obstructive sleep apnea; n (%) 2,556 (10.9%) 2,578 (11.0%) 1,669 (10.3%) 1,660 (10.2%) 1,076 (8.8%) 1,116 (9.1%) 5,301 (10.2%) 5,354 (10.3%) 0.00 Pneumonia; n (%) 274 (1.2%) 277 (1.2%) 134 (0.8%) 137 (0.8%) 205 (1.7%) 199 (1.6%) 613 (1.2%) 613 (1.2%) 0.00 Imaging; n (%) 17 (0.1%) 11 (0.0%) 2 (0.0%) 4 (0.0%) 3 (0.0%) 7 (0.1%) 22 (0.0%) 22 (0.0%) #DIV/0! Diabetes Medications DM Medications - AGIs; n (%) 96 (0.4%) 84 (0.4%) 62 (0.4%) 53 (0.3%) 65 (0.5%) 55 (0.4%) 223 (0.4%) 192 (0.4%) 0.00 DM Medications - Glitazones; n (%) 1,911 (8.2%) 1,918 (8.2%) 1,276 (7.8%) 1,238 (7.6%) 1,122 (9.1%) 1,141 (9.3%) 4,309 (8.3%) 4,297 (8.3%) 0.00 DM Medications - GLP-1 RA; n (%) 2,818 (12.1%) 2,766 (11.8%) 2,504 (15.4%) 2,610 (16.1%) 1,726 (14.1%) 1,727 (14.1%) 7,048 (13.6%) 7,103 (13.7%) 0.00 DM Medications - Insulin; n (%) 5,667 (24.3%) 5,820 (24.9%) 4,304 (26.5%) 4,372 (26.9%) 4,016 (32.7%) 3,979 (32.4%) 13,987 (27.0%) 14,171 (27.3%) -0.01 DM Medications - Meglitinides; n (%) 189 (0.8%) 173 (0.7%) 163 (1.0%) 147 (0.9%) 242 (2.0%) 233 (1.9%) 594 (1.1%) 553 (1.1%) 0.00 DM Medications - Metformin; n (%) 17,574 (75.3%) 17,572 (75.3%) 12,522 (77.0%) 12,557 (77.2%) 8,828 (71.9%) 8,922 (72.7%) 38,924 (75.0%) 39,051 (75.3%) -0.01 Concomitant initiation or current use of 2nd Generation SUs; n (%) 6,872 (29.4%) 6,844 (29.3%) 4,288 (26.4%) 4,204 (25.9%) 3,984 (32.5%) 4,005 (32.6%) 15,144 (29.2%) 15,053 (29.0%) 0.00 Concomitant initiation or current use of AGIs; n (%) 34 (0.1%) 62 (0.3%) 18 (0.1%) 37 (0.2%) 38 (0.3%) 33 (0.3%) 090 (0.2%) 132 (0.3%) -0.02 Concomitant initiation or current use of Glitazones; n (%) 1,491 (6.4%) 1,502 (6.4%) 1,021 (6.3%) 1,002 (6.2%) 908 (7.4%) 901 (7.3%) 3,420 (6.6%) 3,405 (6.6%) 0.00 Concomitant initiation or current use of GLP-1 RA; n (%) 1,759 (7.5%) 1,868 (8.0%) 1,628 (10.0%) 1,819 (11.2%) 1,193 (9.7%) 1,188 (9.7%) 4,580 (8.8%) 4,875 (9.4%) -0.02 Concomitant initiation or current use of Insulin; n (%) 4,304 (18.4%) 4,426 (19.0%) 3,246 (20.0%) 3,306 (20.3%) 3,154 (25.7%) 3,143 (25.6%) 10,704 (20.6%) 10,875 (21.0%) -0.01 Concomitant initiation or current use of Meglitinides; n (%) 69 (0.3%) 133 (0.6%) 36 (0.2%) 113 (0.7%) 163 (1.3%) 162 (1.3%) 268 (0.5%) 408 (0.8%) -0.04 Concomitant initiation or current use of Metformin; n (%) 14,453 (61.9%) 14,426 (61.8%) 10,402 (64.0%) 10,439 (64.2%) 7,405 (60.3%) 7,479 (60.9%) 32,260 (62.2%) 32,344 (62.3%) 0.00 Past use of 2nd Generation SUs Copy; n (%) 1,765 (7.6%) 1,760 (7.5%) 1,106 (6.8%) 1,102 (6.8%) 871 (7.1%) 857 (7.0%) 3,742 (7.2%) 3,719 (7.2%) 0.00 Past use of AGIs Copy; n (%) 62 (0.3%) 22 (0.1%) 44 (0.3%) 16 (0.1%) 27 (0.2%) 22 (0.2%) 133 (0.3%) 060 (0.1%) 0.04 Past use of Glitazones Copy; n (%) 420 (1.8%) 416 (1.8%) 255 (1.6%) 236 (1.5%) 214 (1.7%) 240 (2.0%) 889 (1.7%) 892 (1.7%) 0.00 Past use of GLP-1 RA Copy; n (%) 1,125 (4.8%) 1,105 (4.7%) 938 (5.8%) 929 (5.7%) 533 (4.3%) 539 (4.4%) 2,596 (5.0%) 2,573 (5.0%) 0.00 Past use of Insulin Copy; n (%) 1,363 (5.8%) 1,394 (6.0%) 1,059 (6.5%) 1,066 (6.6%) 862 (7.0%) 836 (6.8%) 3,284 (6.3%) 3,296 (6.4%) 0.00 Past use of Meglitinides Copy; n (%) 120 (0.5%) 40 (0.2%) 127 (0.8%) 34 (0.2%) 79 (0.6%) 71 (0.6%) 326 (0.6%) 145 (0.3%) 0.04 Past use of metformin (final) Copy; n (%) 3,121 (13.4%) 3,146 (13.5%) 2,120 (13.0%) 2,118 (13.0%) 1,423 (11.6%) 1,443 (11.8%) 6,664 (12.8%) 6,707 (12.9%) 0.00 Other Medications Use of ACE inhibitors; n (%) 12,630 (54.1%) 12,632 (54.1%) 9,020 (55.5%) 9,058 (55.7%) 5,901 (48.1%) 5,809 (47.3%) 27,551 (53.1%) 27,499 (53.0%) 0.00 Use of ARBs; n (%) 7,938 (34.0%) 7,860 (33.7%) 5,473 (33.7%) 5,489 (33.8%) 4,415 (36.0%) 4,450 (36.3%) 17,826 (34.4%) 17,799 (34.3%) 0.00 Use of Loop Diuretics - United; n (%) 1,943 (8.3%) 1,984 (8.5%) 904 (5.6%) 901 (5.5%) 1,646 (13.4%) 1,632 (13.3%) 4,493 (8.7%) 4,517 (8.7%) 0.00 Use of other diuretics- United; n (%) 662 (2.8%) 665 (2.8%) 377 (2.3%) 386 (2.4%) 455 (3.7%) 450 (3.7%) 1,494 (2.9%) 1,501 (2.9%) 0.00 Use of nitrates-United; n (%) 1,133 (4.9%) 1,162 (5.0%) 528 (3.2%) 518 (3.2%) 904 (7.4%) 925 (7.5%) 2,565 (4.9%) 2,605 (5.0%) 0.00 Use of other hypertension drugs; n (%) 1,107 (4.7%) 1,112 (4.8%) 551 (3.4%) 568 (3.5%) 773 (6.3%) 766 (6.2%) 2,431 (4.7%) 2,446 (4.7%) 0.00 Use of digoxin- United; n (%) 232 (1.0%) 241 (1.0%) 104 (0.6%) 99 (0.6%) 270 (2.2%) 294 (2.4%) 606 (1.2%) 634 (1.2%) 0.00 Use of Anti-arrhythmics; n (%) 247 (1.1%) 249 (1.1%) 104 (0.6%) 122 (0.8%) 199 (1.6%) 205 (1.7%) 550 (1.1%) 576 (1.1%) 0.00 Use of COPD/asthma meds- United; n (%) 3,029 (13.0%) 3,079 (13.2%) 2,104 (12.9%) 2,072 (12.7%) 1,953 (15.9%) 1,944 (15.8%) 7,086 (13.7%) 7,095 (13.7%) 0.00 Use of statins; n (%) 16,944 (72.6%) 17,094 (73.2%) 11,249 (69.2%) 11,305 (69.5%) 9,472 (77.2%) 9,578 (78.0%) 37,665 (72.6%) 37,977 (73.2%) -0.01 Use of other lipid-lowering drugs; n (%) 2,712 (11.6%) 2,719 (11.6%) 2,265 (13.9%) 2,251 (13.8%) 1,703 (13.9%) 1,748 (14.2%) 6,680 (12.9%) 6,718 (13.0%) 0.00 Use of antiplatelet agents; n (%) 2,966 (12.7%) 3,091 (13.2%) 1,685 (10.4%) 1,720 (10.6%) 2,062 (16.8%) 2,094 (17.1%) 6,713 (12.9%) 6,905 (13.3%) -0.01 Use of oral anticoagulants (Dabigatran, Rivaroxaban, Apixaban, Warfarin); n (%) 1,122 (4.8%) 1,113 (4.8%) 487 (3.0%) 496 (3.1%) 1,039 (8.5%) 1,046 (8.5%) 2,648 (5.1%) 2,655 (5.1%) 0.00 Use of heparin and other low-molecular weight heparins; n (%) 36 (0.2%) 39 (0.2%) 2 (0.0%) 1 (0.0%) 26 (0.2%) 19 (0.2%) 064 (0.1%) 059 (0.1%) 0.00 Use of NSAIDs; n (%) 3,960 (17.0%) 3,882 (16.6%) 2,758 (17.0%) 2,715 (16.7%) 1,805 (14.7%) 1,827 (14.9%) 8,523 (16.4%) 8,424 (16.2%) 0.01 Use of oral corticosteroids; n (%) 2,383 (10.2%) 2,420 (10.4%) 1,565 (9.6%) 1,499 (9.2%) 1,393 (11.4%) 1,402 (11.4%) 5,341 (10.3%) 5,321 (10.3%) 0.00 Use of bisphosphonate (United); n (%) 316 (1.4%) 298 (1.3%) 51 (0.3%) 64 (0.4%) 234 (1.9%) 244 (2.0%) 601 (1.2%) 606 (1.2%) 0.00 Use of opioids- United; n (%) 4,735 (20.3%) 4,673 (20.0%) 3,066 (18.9%) 3,075 (18.9%) 2,459 (20.0%) 2,396 (19.5%) 10,260 (19.8%) 10,144 (19.6%) 0.01 Use of antidepressants; n (%) 5,428 (23.2%) 5,472 (23.4%) 3,600 (22.1%) 3,559 (21.9%) 3,017 (24.6%) 2,934 (23.9%) 12,045 (23.2%) 11,965 (23.1%) 0.00 Use of antipsychotics; n (%) 495 (2.1%) 473 (2.0%) 201 (1.2%) 224 (1.4%) 245 (2.0%) 242 (2.0%) 941 (1.8%) 939 (1.8%) 0.00 Use of anticonvulsants; n (%) 3,847 (16.5%) 3,812 (16.3%) 1,838 (11.3%) 1,857 (11.4%) 1,963 (16.0%) 2,017 (16.4%) 7,648 (14.7%) 7,686 (14.8%) 0.00 Use of lithium- United; n (%) 45 (0.2%) 34 (0.1%) 20 (0.1%) 23 (0.1%) 10 (0.1%) 8 (0.1%) 075 (0.1%) 065 (0.1%) 0.00 Use of Benzos- United; n (%) 2,138 (9.2%) 2,112 (9.0%) 1,332 (8.2%) 1,355 (8.3%) 1,190 (9.7%) 1,191 (9.7%) 4,660 (9.0%) 4,658 (9.0%) 0.00 Use of anxiolytics/hypnotics- United; n (%) 1,177 (5.0%) 1,179 (5.0%) 895 (5.5%) 907 (5.6%) 659 (5.4%) 633 (5.2%) 2,731 (5.3%) 2,719 (5.2%) 0.00 Use of dementia meds- United; n (%) 196 (0.8%) 200 (0.9%) 47 (0.3%) 49 (0.3%) 280 (2.3%) 263 (2.1%) 523 (1.0%) 512 (1.0%) 0.00 Use of antiparkinsonian meds- United; n (%) 490 (2.1%) 464 (2.0%) 219 (1.3%) 223 (1.4%) 307 (2.5%) 301 (2.5%) 1,016 (2.0%) 988 (1.9%) 0.01 Any use of pramlintide; n (%) 1 (0.0%) 8 (0.0%) 4 (0.0%) 19 (0.1%) 1 (0.0%) 6 (0.0%) 006 (0.0%) 033 (0.1%) -0.04 Any use of 1st generation sulfonylureas; n (%) 1 (0.0%) 1 (0.0%) 1 (0.0%) 1 (0.0%) 0 (0.0%) 1 (0.0%) 002 (0.0%) 003 (0.0%) 0.00 Entresto (sacubitril/valsartan); n (%) 61 (0.3%) 85 (0.4%) 11 (0.1%) 17 (0.1%) 27 (0.2%) 38 (0.3%) 099 (0.2%) 140 (0.3%) 0.00 Initiation as monotherapy v4 Copy; n (%) 21,745 (93.1%) 21,734 (93.1%) 15,358 (94.5%) 15,280 (94.0%) 11,660 (95.0%) 11,681 (95.2%) 48,763 (94.0%) 48,695 (93.9%) 0.00 Labs 39,604 39,604 Lab values- HbA1c (%) v3; n (%) 9,831 (42.1%) 9,665 (41.4%) 1,205 (7.4%) 875 (5.4%) N/A N/A 11,036 (27.9%) 10,540 (26.6%) 0.03 Lab values- HbA1c (%) (within 3 months) v3; n (%) 7,941 (34.0%) 7,797 (33.4%) 974 (6.0%) 717 (4.4%) N/A N/A 8,915 (22.5%) 8,514 (21.5%) 0.02 Lab values- HbA1c (%) (within 6 months) v3; n (%) 9,831 (42.1%) 9,665 (41.4%) 1,205 (7.4%) 875 (5.4%) N/A N/A 11,036 (27.9%) 10,540 (26.6%) 0.03 Lab values- BNP; n (%) 124 (0.5%) 131 (0.6%) 9 (0.1%) 4 (0.0%) N/A N/A 133 (0.3%) 135 (0.3%) 0.00 Lab values- BNP (within 3 months); n (%) 87 (0.4%) 82 (0.4%) 6 (0.0%) 1 (0.0%) N/A N/A 093 (0.2%) 083 (0.2%) 0.00 Lab values- BNP (within 6 months); n (%) 124 (0.5%) 131 (0.6%) 9 (0.1%) 4 (0.0%) N/A N/A 133 (0.3%) 135 (0.3%) 0.00 Lab values- BUN (mg/dl); n (%) 9,643 (41.3%) 9,318 (39.9%) 1,133 (7.0%) 804 (4.9%) N/A N/A 10,776 (27.2%) 10,122 (25.6%) 0.04 Lab values- BUN (mg/dl) (within 3 months); n (%) 7,601 (32.6%) 7,350 (31.5%) 888 (5.5%) 653 (4.0%) N/A N/A 8,489 (21.4%) 8,003 (20.2%) 0.03 Lab values- BUN (mg/dl) (within 6 months); n (%) 9,643 (41.3%) 9,318 (39.9%) 1,133 (7.0%) 804 (4.9%) N/A N/A 10,776 (27.2%) 10,122 (25.6%) 0.04 Lab values- Creatinine (mg/dl) v2; n (%) 10,061 (43.1%) 9,817 (42.0%) 1,246 (7.7%) 907 (5.6%) N/A N/A 11,307 (28.6%) 10,724 (27.1%) 0.03 Lab values- Creatinine (mg/dl) (within 3 months) v2; n (%) 7,936 (34.0%) 7,732 (33.1%) 977 (6.0%) 734 (4.5%) N/A N/A 8,913 (22.5%) 8,466 (21.4%) 0.03 Lab values- Creatinine (mg/dl) (within 6 months) v2; n (%) 10,061 (43.1%) 9,817 (42.0%) 1,246 (7.7%) 907 (5.6%) N/A N/A 11,307 (28.6%) 10,724 (27.1%) 0.03 Lab values- HDL level (mg/dl); n (%) 8,627 (36.9%) 8,258 (35.4%) 1,123 (6.9%) 831 (5.1%) N/A N/A 9,750 (24.6%) 9,089 (22.9%) 0.04

Lab values- HDL level (mg/dl) (within 3 months); n (%) 6,442 (27.6%) 6,191 (26.5%) 829 (5.1%) 642 (3.9%) N/A N/A 7,271 (18.4%) 6,833 (17.3%) 0.03

Lab values- HDL level (mg/dl) (within 6 months); n (%) 8,627 (36.9%) 8,258 (35.4%) 1,123 (6.9%) 831 (5.1%) N/A N/A 9,750 (24.6%) 9,089 (22.9%) 0.04 Lab values- LDL level (mg/dl) v2; n (%) 8,884 (38.1%) 8,528 (36.5%) 1,151 (7.1%) 821 (5.1%) N/A N/A 10,035 (25.3%) 9,349 (23.6%) 0.04 Lab values- LDL level (mg/dl) (within 3 months) v2; n (%) 6,631 (28.4%) 6,393 (27.4%) 846 (5.2%) 638 (3.9%) N/A N/A 7,477 (18.9%) 7,031 (17.8%) 0.03 Lab values- LDL level (mg/dl) (within 6 months) v2; n (%) 8,884 (38.1%) 8,528 (36.5%) 1,151 (7.1%) 821 (5.1%) N/A N/A 10,035 (25.3%) 9,349 (23.6%) 0.04 Lab values- NT-proBNP; n (%) 21 (0.1%) 35 (0.1%) 2 (0.0%) 2 (0.0%) N/A N/A 23 (0.1%) 0 (0.1%) - Lab values- NT-proBNP (within 3 months); n (%) 12 (0.1%) 23 (0.1%) 1 (0.0%) 2 (0.0%) N/A N/A 13 (0.0%) 0 (0.1%) - Lab values- NT-proBNP (within 6 months); n (%) 21 (0.1%) 35 (0.1%) 2 (0.0%) 2 (0.0%) N/A N/A 23 (0.1%) 37 (0.1%) - Lab values- Total cholesterol (mg/dl) v2; n (%) 8,784 (37.6%) 8,440 (36.1%) 1,128 (6.9%) 843 (5.2%) N/A N/A 9,912 (25.0%) 9,283 (23.4%) 0.04 Lab values- Total cholesterol (mg/dl) (within 3 months) v2; n (%) 6,572 (28.1%) 6,328 (27.1%) 834 (5.1%) 655 (4.0%) N/A N/A 7,406 (18.7%) 6,983 (17.6%) 0.03 Lab values- Total cholesterol (mg/dl) (within 6 months) v2; n (%) 8,784 (37.6%) 8,440 (36.1%) 1,128 (6.9%) 843 (5.2%) N/A N/A 9,912 (25.0%) 9,283 (23.4%) 0.04 Lab values- Triglyceride level (mg/dl); n (%) 8,729 (37.4%) 8,387 (35.9%) 1,107 (6.8%) 830 (5.1%) N/A N/A 9,836 (24.8%) 9,217 (23.3%) 0.04 Lab values- Triglyceride level (mg/dl) (within 3 months); n (%) 6,532 (28.0%) 6,292 (26.9%) 819 (5.0%) 645 (4.0%) N/A N/A 7,351 (18.6%) 6,937 (17.5%) 0.03 Lab values- Triglyceride level (mg/dl) (within 6 months); n (%) 8,729 (37.4%) 8,387 (35.9%) 1,107 (6.8%) 830 (5.1%) N/A N/A 9,836 (24.8%) 9,217 (23.3%) 0.04 Lab result number- HbA1c (%) mean (only 2 to 20 included) v4 9,775 9,615 1,174 849 N/A N/A 10,949 10,464 ...mean (sd) 8.54 (1.81) 8.53 (1.74) 8.55 (1.86) 8.35 (1.84) N/A N/A 8.54 (1.82) 8.52 (1.75) 0.01 ...median [IQR] 8.20 [7.30, 9.50] 8.20 [7.30, 9.50] 8.02 [7.10, 9.60] 8.00 [7.00, 9.05] N/A N/A 8.18 (1.82) 8.18 (1.75) 0.00 ...Missing; n (%) 13,573 (58.1%) 13,733 (58.8%) 15,082 (92.8%) 15,407 (94.8%) N/A N/A 28,655 (72.4%) 29,140 (73.6%) -0.03 Lab result number- BNP mean v2 124 131 9 4 N/A N/A 133 135 ...mean (sd) 112.01 (210.30) 157.77 (558.63) 212.09 (296.53) 34.75 (39.73) N/A N/A 118.78 (217.38) 154.12 (554.41) -0.08 ...median [IQR] 46.35 [21.48, 119.75] 34.30 [15.10, 85.90] 82.00 [18.50, 390.17] 18.00 [11.25, 75.00] N/A N/A #VALUE! #VALUE! #VALUE! ...Missing; n (%) 23,224 (99.5%) 23,217 (99.4%) 16,247 (99.9%) 16,252 (100.0%) N/A N/A 39,471 (99.7%) 39,469 (99.7%) 0.00 Lab result number- BUN (mg/dl) mean v2 9,643 9,318 1,133 804 N/A N/A 10,776 10,122 ...mean (sd) 16.88 (6.53) 16.67 (5.66) 2,699.09 (19,836.99) 2,092.82 (18,091.72) N/A N/A 298.89 (6430.29) 181.58 (5096.47) 0.02 ...median [IQR] 15.75 [12.83, 20.00] 16.00 [13.00, 19.50] 15.00 [12.00, 19.00] 15.50 [13.00, 19.00] N/A N/A #VALUE! #VALUE! #VALUE! ...Missing; n (%) 13,705 (58.7%) 14,030 (60.1%) 15,123 (93.0%) 15,452 (95.1%) N/A N/A 28,828 (72.8%) 29,482 (74.4%) -0.04 Lab result number- Creatinine (mg/dl) mean (only 0.1 to 15 included) v3 9,998 9,755 895 602 N/A N/A 10,893 10,357 ...mean (sd) 0.97 (0.34) 0.92 (0.24) 0.97 (0.32) 0.93 (0.20) N/A N/A 0.97 (0.34) 0.92 (0.24) 0.17 ...median [IQR] 0.90 [0.77, 1.09] 0.89 [0.75, 1.05] 0.99 [0.80, 1.03] 0.94 [0.80, 1.00] N/A N/A 0.91 (0.34) 0.89 (0.24) 0.07 ...Missing; n (%) 13,350 (57.2%) 13,593 (58.2%) 15,361 (94.5%) 15,654 (96.3%) N/A N/A 28,711 (72.5%) 29,247 (73.8%) -0.03 Lab result number- HDL level (mg/dl) mean (only =<5000 included) v2 8,627 8,258 1,110 823 N/A N/A 9,737 9,081 ...mean (sd) 44.52 (12.71) 44.58 (12.97) 43.52 (13.91) 43.88 (14.00) N/A N/A 44.41 (12.85) 44.52 (13.07) -0.01 ...median [IQR] 43.00 [36.00, 51.00] 43.00 [36.00, 51.00] 42.00 [35.00, 51.00] 42.00 [35.00, 50.00] N/A N/A 42.89 (12.85) 42.91 (13.07) 0.00 ...Missing; n (%) 14,721 (63.1%) 15,090 (64.6%) 15,146 (93.2%) 15,433 (94.9%) N/A N/A 29,867 (75.4%) 30,523 (77.1%) -0.04 Lab result number- LDL level (mg/dl) mean (only =<5000 included) v2 8,749 8,391 1,051 759 N/A N/A 9,800 9,150 ...mean (sd) 84.74 (40.98) 82.44 (40.44) 88.10 (42.19) 85.51 (40.99) N/A N/A 85.10 (41.11) 82.69 (40.49) 0.06 ...median [IQR] 83.00 [61.00, 108.00] 81.00 [59.00, 106.00] 87.00 [65.00, 114.00] 85.00 [62.00, 109.50] N/A N/A 83.43 (41.11) 81.33 (40.49) 0.05 ...Missing; n (%) 14,599 (62.5%) 14,957 (64.1%) 15,205 (93.5%) 15,497 (95.3%) N/A N/A 29,804 (75.3%) 30,454 (76.9%) -0.04 Lab result number- Total cholesterol (mg/dl) mean (only =<5000 included) v2 8,781 8,437 1,115 833 N/A N/A 9,896 9,270 ...mean (sd) 174.25 (50.27) 171.08 (46.33) 177.60 (48.87) 172.86 (50.20) N/A N/A 174.63 (50.12) 171.24 (46.69) 0.07 ...median [IQR] 167.00 [142.00, 198.00] 166.00 [140.00, 195.00] 173.00 [146.00, 202.50] 166.00 [141.00, 197.00] N/A N/A 167.68 (50.12) 166.00 (46.69) 0.03 ...Missing; n (%) 14,567 (62.4%) 14,911 (63.9%) 15,141 (93.1%) 15,423 (94.9%) N/A N/A 29,708 (75.0%) 30,334 (76.6%) -0.04 Lab result number- Triglyceride level (mg/dl) mean (only =<5000 included) v2 8,727 8,386 1,094 820 N/A N/A 9,821 9,206 ...mean (sd) 206.03 (209.48) 205.13 (195.93) 205.85 (192.00) 207.65 (208.83) N/A N/A 206.01 (207.62) 205.35 (197.12) 0.00 ...median [IQR] 160.00 [112.50, 233.00] 159.00 [113.00, 235.00] 158.00 [107.75, 236.00] 155.50 [107.12, 230.50] N/A N/A 159.78 (207.62) 158.69 (197.12) 0.01 ...Missing; n (%) 14,621 (62.6%) 14,962 (64.1%) 15,162 (93.3%) 15,436 (95.0%) N/A N/A 29,783 (75.2%) 30,398 (76.8%) -0.04 Lab result number- Hemoglobin mean (only >0 included) 6,623 6,297 746 539 N/A N/A 7,369 6,836 ...mean (sd) 13.95 (1.54) 14.12 (1.48) 2,009.61 (16,579.76) 2,036.03 (16,533.04) N/A N/A 215.98 (5272.79) 173.54 (4639.15) 0.01 ...median [IQR] 13.97 [12.90, 15.00] 14.10 [13.10, 15.15] 14.00 [12.90, 15.00] 14.00 [13.00, 15.00] N/A N/A #VALUE! #VALUE! #VALUE! ...Missing; n (%) 16,725 (71.6%) 17,051 (73.0%) 15,510 (95.4%) 15,717 (96.7%) N/A N/A 32,235 (81.4%) 32,768 (82.7%) -0.03 Lab result number- Serum sodium mean (only > 90 and < 190 included) 9,809 9,555 1,169 844 N/A N/A 10,978 10,399 ...mean (sd) 139.38 (2.72) 139.45 (2.69) 138.84 (2.47) 139.11 (2.56) N/A N/A 139.32 (2.69) 139.42 (2.68) -0.04 ...median [IQR] 139.50 [138.00, 141.00] 139.50 [138.00, 141.00] 139.00 [137.00, 140.50] 139.00 [137.00, 141.00] N/A N/A 139.45 (2.69) 139.46 (2.68) 0.00 ...Missing; n (%) 13,539 (58.0%) 13,793 (59.1%) 15,087 (92.8%) 15,412 (94.8%) N/A N/A 28,626 (72.3%) 29,205 (73.7%) -0.03 Lab result number- Albumin mean (only >0 and <=10 included) 9,316 8,998 994 699 N/A N/A 10,310 9,697 ...mean (sd) 4.31 (0.31) 4.32 (0.31) 4.11 (0.40) 4.11 (0.40) N/A N/A 4.29 (0.32) 4.30 (0.32) -0.03 ...median [IQR] 4.30 [4.10, 4.50] 4.30 [4.10, 4.50] 4.00 [4.00, 4.30] 4.00 [4.00, 4.30] N/A N/A 4.27 (0.32) 4.28 (0.32) -0.03 ...Missing; n (%) 14,032 (60.1%) 14,350 (61.5%) 15,262 (93.9%) 15,557 (95.7%) N/A N/A 29,294 (74.0%) 29,907 (75.5%) -0.03 Lab result number- Glucose (fasting or random) mean (only 10-1000 included) 9,842 9,589 1,194 866 N/A N/A 11,036 10,455 ...mean (sd) 185.19 (75.07) 182.71 (71.43) 187.05 (74.89) 178.59 (71.11) N/A N/A 185.39 (75.05) 182.37 (71.41) 0.04 ...median [IQR] 167.33 [133.00, 221.67] 167.50 [133.00, 217.00] 168.00 [134.00, 223.00] 161.50 [128.88, 209.62] N/A N/A 167.40 (75.05) 167.00 (71.41) 0.01 ...Missing; n (%) 13,506 (57.8%) 13,759 (58.9%) 15,062 (92.7%) 15,390 (94.7%) N/A N/A 28,568 (72.1%) 29,149 (73.6%) -0.03 Lab result number- Potassium mean (only 1-7 included) 10,007 9,760 1,121 803 N/A N/A 11,128 10,563 ...mean (sd) 4.48 (0.41) 4.47 (0.41) 4.23 (0.49) 4.17 (0.51) N/A N/A 4.45 (0.42) 4.45 (0.42) 0.00 ...median [IQR] 4.50 [4.20, 4.70] 4.45 [4.20, 4.70] 4.20 [4.00, 4.50] 4.00 [4.00, 4.50] N/A N/A 4.47 (0.42) 4.42 (0.42) 0.12 ...Missing; n (%) 13,341 (57.1%) 13,588 (58.2%) 15,135 (93.1%) 15,453 (95.1%) N/A N/A 28,476 (71.9%) 29,041 (73.3%) -0.03 Comorbidity Scores CCI (180 days)- ICD9 and ICD10 v2 ...mean (sd) 2.24 (1.51) 2.25 (1.50) 1.64 (1.09) 1.64 (1.08) 2.46 (1.60) 2.46 (1.58) 2.10 (1.42) 2.11 (1.40) -0.01 ...median [IQR] 2.00 [1.00, 3.00] 2.00 [1.00, 3.00] 1.00 [1.00, 2.00] 2.00 [1.00, 2.00] 2.00 [1.00, 3.00] 2.00 [1.00, 3.00] 1.69 (1.42) 2.00 (1.40) -0.22 Frailty Score: Qualitative Version 365 days as Categories, v1 ...0; n (%) 19,819 (84.9%) 19,899 (85.2%) 12,360 (76.0%) 12,390 (76.2%) 9,196 (74.9%) 9,211 (75.1%) 41,375 (79.8%) 41,500 (80.0%) 0.00 ...1 to 2; n (%) 3,110 (13.3%) 3,047 (13.1%) 3,226 (19.8%) 3,277 (20.2%) 2,192 (17.9%) 2,242 (18.3%) 8,528 (16.4%) 8,566 (16.5%) 0.00 ...3 or more; n (%) 419 (1.8%) 402 (1.7%) 670 (4.1%) 589 (3.6%) 884 (7.2%) 819 (6.7%) 1,973 (3.8%) 1,810 (3.5%) 0.02 Frailty Score: Empirical Version 365 days as Categories, v3 ...< 0.12908; n (%) 7,772 (33.3%) 7,781 (33.3%) 5,983 (36.8%) 5,968 (36.7%) 2,071 (16.9%) 2,018 (16.4%) 15,826 (30.5%) 15,767 (30.4%) 0.00 ...0.12908 - 0.1631167; n (%) 8,197 (35.1%) 8,178 (35.0%) 6,230 (38.3%) 6,257 (38.5%) 3,812 (31.1%) 3,887 (31.7%) 18,239 (35.2%) 18,322 (35.3%) 0.00 ...>= 0.1631167; n (%) 7,379 (31.6%) 7,389 (31.6%) 4,043 (24.9%) 4,031 (24.8%) 6,389 (52.1%) 6,367 (51.9%) 17,811 (34.3%) 17,787 (34.3%) 0.00 Non-Frailty; n (%) 13,684 (58.6%) 13,885 (59.5%) 8,676 (53.4%) 8,682 (53.4%) 687 (5.6%) 574 (4.7%) 23,047 (44.4%) 23,141 (44.6%) 0.00

Frailty Score (mean): Qualitative Version 365 days, v1 ...mean (sd) 0.23 (0.69) 0.22 (0.67) 0.41 (0.91) 0.39 (0.88) 0.52 (1.18) 0.50 (1.13) 0.36 (0.90) 0.34 (0.86) 0.02 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 1.00] 0.00 [0.00, 0.00] 0.00 (0.90) 0.00 (0.86) 0.00 Frailty Score (mean): Empirical Version 365 days, v2 ...mean (sd) 0.15 (0.04) 0.15 (0.04) 0.14 (0.03) 0.14 (0.03) 0.17 (0.05) 0.17 (0.05) 0.15 (0.04) 0.15 (0.04) 0.00 ...median [IQR] 0.14 [0.12, 0.17] 0.14 [0.12, 0.17] 0.13 [0.12, 0.16] 0.13 [0.12, 0.16] 0.17 [0.14, 0.20] 0.17 [0.14, 0.20] 0.14 (0.04) 0.14 (0.04) 0.00 Healthcare Utilization Any hospitalization; n (%) 942 (4.0%) 943 (4.0%) 370 (2.3%) 357 (2.2%) 459 (3.7%) 452 (3.7%) 1,771 (3.4%) 1,752 (3.4%) 0.00 Any hospitalization within prior 30 days; n (%) 260 (1.1%) 253 (1.1%) 47 (0.3%) 59 (0.4%) 62 (0.5%) 62 (0.5%) 369 (0.7%) 374 (0.7%) 0.00 Any hospitalization during prior 31-180 days; n (%) 707 (3.0%) 718 (3.1%) 324 (2.0%) 304 (1.9%) 406 (3.3%) 396 (3.2%) 1,437 (2.8%) 1,418 (2.7%) 0.01 Endocrinologist Visit; n (%) 3,724 (15.9%) 3,906 (16.7%) 2,816 (17.3%) 3,105 (19.1%) 2,876 (23.4%) 2,909 (23.7%) 9,416 (18.2%) 9,920 (19.1%) -0.02 Endocrinologist Visit (30 days prior); n (%) 2,742 (11.7%) 2,824 (12.1%) 2,148 (13.2%) 2,248 (13.8%) 2,148 (17.5%) 2,203 (18.0%) 7,038 (13.6%) 7,275 (14.0%) -0.01 Endocrinologist Visit (31 to 180 days prior); n (%) 2,547 (10.9%) 2,566 (11.0%) 1,961 (12.1%) 2,024 (12.5%) 2,132 (17.4%) 2,105 (17.2%) 6,640 (12.8%) 6,695 (12.9%) 0.00 Internal medicine/family medicine visits; n (%) 17,315 (74.2%) 17,090 (73.2%) 14,028 (86.3%) 13,914 (85.6%) 9,841 (80.2%) 9,803 (79.9%) 41,184 (79.4%) 40,807 (78.7%) 0.02 Internal medicine/family medicine visits (30 days prior) v2; n (%) 12,759 (54.6%) 12,630 (54.1%) 10,312 (63.4%) 10,170 (62.6%) 6,821 (55.6%) 6,822 (55.6%) 29,892 (57.6%) 29,622 (57.1%) 0.01 Internal medicine/family medicine visits (31 to 180 days prior) v2; n (%) 14,658 (62.8%) 14,675 (62.9%) 11,571 (71.2%) 11,534 (71.0%) 8,648 (70.5%) 8,606 (70.1%) 34,877 (67.2%) 34,815 (67.1%) 0.00 Cardiologist visit; n (%) 5,600 (24.0%) 5,633 (24.1%) 2,529 (15.6%) 2,537 (15.6%) 3,896 (31.7%) 3,888 (31.7%) 12,025 (23.2%) 12,058 (23.2%) 0.00 Number of Cardiologist visits (30 days prior); n (%) 2,011 (8.6%) 2,030 (8.7%) 741 (4.6%) 767 (4.7%) 1,284 (10.5%) 1,291 (10.5%) 4,036 (7.8%) 4,088 (7.9%) 0.00 Number of Cardiologist visits (31 to 180 days prior); n (%) 4,653 (19.9%) 4,685 (20.1%) 2,165 (13.3%) 2,135 (13.1%) 3,363 (27.4%) 3,349 (27.3%) 10,181 (19.6%) 10,169 (19.6%) 0.00 Electrocardiogram v2; n (%) 6,041 (25.9%) 6,080 (26.0%) 3,536 (21.8%) 3,516 (21.6%) 3,770 (30.7%) 3,807 (31.0%) 13,347 (25.7%) 13,403 (25.8%) 0.00 Use of glucose test strips; n (%) 733 (3.1%) 729 (3.1%) 660 (4.1%) 618 (3.8%) 385 (3.1%) 375 (3.1%) 1,778 (3.4%) 1,722 (3.3%) 0.01 Dialysis; n (%) 1 (0.0%) 1 (0.0%) 0 (0.0%) 0 (0.0%) 1 (0.0%) 1 (0.0%) 002 (0.0%) 002 (0.0%) #DIV/0! Naive new user v8 Copy; n (%) 1,833 (7.9%) 1,838 (7.9%) 1,070 (6.6%) 1,086 (6.7%) 683 (5.6%) 645 (5.3%) 3,586 (6.9%) 3,569 (6.9%) 0.00 N antidiabetic drugs at index date v3 Copy ...mean (sd) 2.25 (0.83) 2.26 (0.89) 2.28 (0.85) 2.30 (0.92) 2.38 (0.88) 2.38 (0.90) 2.29 (0.85) 2.30 (0.90) -0.01 ...median [IQR] 2.00 [2.00, 3.00] 2.00 [2.00, 3.00] 2.00 [2.00, 3.00] 2.00 [2.00, 3.00] 2.00 [2.00, 3.00] 2.00 [2.00, 3.00] 2.00 (0.85) 2.00 (0.90) 0.00 number of different/distinct medication prescriptions ...mean (sd) 10.21 (4.77) 10.23 (4.64) 9.62 (4.33) 9.65 (4.11) 10.46 (4.43) 10.44 (4.19) 10.08 (4.56) 10.10 (4.37) 0.00 ...median [IQR] 9.00 [7.00, 13.00] 9.00 [7.00, 13.00] 9.00 [7.00, 12.00] 9.00 [7.00, 12.00] 10.00 [7.00, 13.00] 10.00 [8.00, 13.00] 9.24 (4.56) 9.24 (4.37) 0.00 Number of Hospitalizations ...mean (sd) 0.05 (0.23) 0.05 (0.24) 0.02 (0.16) 0.02 (0.16) 0.04 (0.23) 0.04 (0.23) 0.04 (0.21) 0.04 (0.22) 0.00 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 (0.21) 0.00 (0.22) 0.00 Number of hospital days ...mean (sd) 0.23 (1.87) 0.22 (1.48) 0.10 (0.90) 0.10 (0.91) 0.20 (1.30) 0.20 (1.29) 0.18 (1.49) 0.18 (1.28) 0.00 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 (1.49) 0.00 (1.28) 0.00 Number of Emergency Department (ED) visits v3 ...mean (sd) 0.31 (0.98) 0.31 (1.14) 0.05 (0.52) 0.05 (0.56) 0.32 (0.97) 0.31 (0.94) 0.23 (0.86) 0.23 (0.94) 0.00 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 (0.86) 0.00 (0.94) 0.00 Number of Office visits ...mean (sd) 4.54 (3.53) 4.54 (3.36) 4.04 (3.12) 4.05 (3.05) 5.33 (3.78) 5.31 (3.64) 4.57 (3.47) 4.57 (3.34) 0.00 ...median [IQR] 4.00 [2.00, 6.00] 4.00 [2.00, 6.00] 3.00 [2.00, 5.00] 3.00 [2.00, 5.00] 4.00 [3.00, 7.00] 4.00 [3.00, 7.00] 3.69 (3.47) 3.69 (3.34) 0.00 Number of Endocrinologist visits ...mean (sd) 0.77 (2.71) 0.83 (2.91) 0.85 (3.07) 0.92 (3.00) 1.25 (3.91) 1.37 (4.56) 0.91 (3.14) 0.99 (3.40) -0.02 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 (3.14) 0.00 (3.40) 0.00 Number of internal medicine/family medicine visits ...mean (sd) 7.64 (11.30) 7.35 (10.72) 6.36 (7.53) 6.21 (7.40) 6.61 (9.32) 6.65 (8.74) 7.00 (9.79) 6.83 (9.32) 0.02 ...median [IQR] 4.00 [0.00, 10.00] 4.00 [0.00, 10.00] 4.00 [2.00, 9.00] 4.00 [2.00, 8.00] 4.00 [1.00, 9.00] 4.00 [1.00, 9.00] 4.00 (9.79) 4.00 (9.32) 0.00 Number of Cardiologist visits ...mean (sd) 1.11 (3.31) 1.13 (3.39) 0.61 (2.22) 0.58 (2.08) 1.43 (3.55) 1.48 (3.91) 1.03 (3.08) 1.04 (3.19) 0.00 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 1.00] 0.00 [0.00, 1.00] 0.00 (3.08) 0.00 (3.19) 0.00 Number electrocardiograms received v2 ...mean (sd) 0.46 (1.13) 0.47 (1.16) 0.34 (0.83) 0.34 (0.84) 0.56 (1.16) 0.55 (1.13) 0.45 (1.05) 0.45 (1.06) 0.00 ...median [IQR] 0.00 [0.00, 1.00] 0.00 [0.00, 1.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 1.00] 0.00 [0.00, 1.00] 0.00 (1.05) 0.00 (1.06) 0.00 Number of HbA1c tests ordered ...mean (sd) 1.35 (0.88) 1.34 (0.86) 1.29 (0.86) 1.29 (0.81) 1.56 (0.86) 1.55 (0.80) 1.38 (0.87) 1.37 (0.83) 0.01 ...median [IQR] 1.00 [1.00, 2.00] 1.00 [1.00, 2.00] 1.00 [1.00, 2.00] 1.00 [1.00, 2.00] 2.00 [1.00, 2.00] 2.00 [1.00, 2.00] 1.24 (0.87) 1.24 (0.83) 0.00 Number of glucose tests ordered ...mean (sd) 0.45 (1.22) 0.44 (1.65) 0.42 (1.25) 0.40 (1.22) 0.46 (1.05) 0.46 (1.07) 0.44 (1.19) 0.43 (1.40) 0.01 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 (1.19) 0.00 (1.40) 0.00 Number of lipid tests ordered ...mean (sd) 1.01 (0.90) 1.00 (0.93) 1.02 (1.20) 1.03 (1.13) 1.07 (0.84) 1.06 (0.82) 1.03 (0.99) 1.02 (0.97) 0.01 ...median [IQR] 1.00 [0.00, 1.00] 1.00 [0.00, 1.00] 1.00 [0.00, 1.00] 1.00 [0.00, 1.00] 1.00 [1.00, 2.00] 1.00 [1.00, 2.00] 1.00 (0.99) 1.00 (0.97) 0.00 Number of creatinine tests ordered ...mean (sd) 0.04 (0.26) 0.04 (0.25) 0.03 (0.22) 0.03 (0.23) 0.06 (0.32) 0.07 (0.33) 0.04 (0.26) 0.04 (0.27) 0.00 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 (0.26) 0.00 (0.27) 0.00 Number of BUN tests ordered ...mean (sd) 0.02 (0.19) 0.02 (0.17) 0.02 (0.15) 0.02 (0.16) 0.04 (0.26) 0.04 (0.26) 0.02 (0.20) 0.02 (0.19) 0.00 ...median [IQR] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 [0.00, 0.00] 0.00 (0.20) 0.00 (0.19) 0.00 Number of tests for microalbuminuria ...mean (sd) 0.85 (1.18) 0.85 (1.16) 0.77 (1.11) 0.77 (1.10) 0.56 (0.72) 0.55 (0.71) 0.76 (1.07) 0.75 (1.05) 0.01 ...median [IQR] 0.00 [0.00, 2.00] 0.00 [0.00, 2.00] 0.00 [0.00, 2.00] 0.00 [0.00, 2.00] 0.00 [0.00, 1.00] 0.00 [0.00, 1.00] 0.00 (1.07) 0.00 (1.05) 0.00 Total N distinct ICD9/ICD10 diagnoses at the 3rd digit level Copy ...mean (sd) 8.12 (6.77) 8.12 (6.87) 3.86 (3.65) 3.82 (3.74) 8.71 (6.96) 8.70 (7.03) 6.92 (6.02) 6.91 (6.11) 0.00 ...median [IQR] 7.00 [4.00, 11.00] 7.00 [4.00, 11.00] 4.00 [0.00, 6.00] 4.00 [0.00, 6.00] 7.00 [4.00, 12.00] 7.00 [4.00, 12.00] 6.06 (6.02) 6.06 (6.11) 0.00

Use of thiazide; n (%) 2,670 (11.4%) 2,656 (11.4%) 1,690 (10.4%) 1,665 (10.2%) 1,695 (13.8%) 1,671 (13.6%) 6,055 (11.7%) 5,992 (11.6%) 0.00 Use of beta blockers; n (%) 8,248 (35.3%) 8,319 (35.6%) 4,785 (29.4%) 4,857 (29.9%) 5,919 (48.2%) 5,963 (48.6%) 18,952 (36.5%) 19,139 (36.9%) -0.01 Use of calcium channel blockers; n (%) 6,390 (27.4%) 6,370 (27.3%) 0 0 3,755 (30.6%) 3,767 (30.7%) #VALUE! #VALUE! #VALUE!