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Pipeline Drugs And Devices Differ New Drugs and Devices: What is In Depending On What Type Of The Pipeline For Type 1 and Type 2 Diabetes  Etiology  Etiology  Screening and  Screening and Prevention Steven V. Edelman, MD Prevention  Implantable GLP-1 RA Professor of Medicine  Encapsulated islet  Oral GLP-1 University of California San Diego School of Medicine cells Veterans Affairs Medical Center  receptor Founder and Director, Taking Control Of Your Diabetes, a 501(c)3  New glucagons antagonists Not-for-Profit Organization  Artificial  CGM for type 2 Diabetes  SGLT1&2 inhibitors  Most powerful therapy in  Very smart apps type 2 diabetes!

Natural History and Cause Screening: Looking of Type 1 Diabetes Autoimmune condition For Antibodies Putative Trigger 100% making cells of Immune System Dysfunction the pancreas Anyone up to age 45 Circulating Auto Antibodies and (ICA, GAD) with a 1st degree relative Symptoms with type 1 diabetes

Genetic Damage to the Pre-diabetes Diabetes TrialNet predisposition cells of the pancreas Time = months to a few years Pettus J, Edelman SV. (2013) Adjunctive Therapies. In The American Diabetes Association/JDRF Type 1 Diabetes Sourcebook (319-340). VA: American Diabetes Association

Can We Prevent The Immune Attack On The Pancreas? Viacyte Device BLOOD VESSEL

CELLS MEMBRANE

Stem

Taken from Viacyte.com

Using the Devices in Mice Controls Blood Sugars

600  Insulin implants STZ after VC-01 explant, No STZ return of blood to pre-implant levels 500

400

300

200

Blood Glucose (mg/dL) Glucose Blood 100

STZ VC-01 blood glucose control by graft stable 5+ months 0 -42 -14 14 42 70 98 126 154 182 210 238

Time (days post-implant)

9

STEP ONE: Demonstrated Differentiation Into Beta Cells and Age at Diagnosis of T1D Potential for Prolonged Cell Survival

PEC-Encap week 1  Cell survival and You can get type 1 diabetes differentiation into beta- at any age! cells 12 weeks after implant

 Appears safe and well- tolerated

Both: 12-week PEC-Encap in  Encaptra device appears to T1D patient Bottom: dark brown be immune protective as = Nkx6.1 immunoreactivity designed marks endocrine cells  Need to optimize engraftment as it relates to the foreign body response Beck RW, Tamborlane WV, Bergenstal RM, Miller KM, Dubose SN, Hall CA. to the device The T1D Exchange Clinic Registry. J Clin Endocrinol Metab. 2012; 97:4383-9. Latent Autoimmune Diabetes in Adults My Story with Type 1 Diabetes (LADA)

➢ The most missed diagnosis in Diagnosed at the age of 15 diabetes (1970) with the classic symptoms ➢ Type 1 diabetes can occur at any age Thirst Urination ➢ Slower beta-cell destruction (may Weight loss respond briefly to oral agents) Poor wound healing ➢ Typically does not have features Blurry vision of the Metabolic Syndrome Gary Hall Jr. Fatigue ➢ positive for type 1 Olympic Gold Medalist diabetes (GAD auto antibodies) World Record Holder Edelman SV, Henry RR. Diagnosis and management of type 2 diabetes. Edelman SV. Taking control of your diabetes: a patient oriented book on diabetes. Edelman SV. Taking control of your diabetes: a patient oriented book on diabetes. Fifth th Fourth Edition Professional Communications Inc., Greenwich, CT. 54412 pages,Edition. 2013. Professional Communications, Inc., Greenwich, CT. 288 pages, 2014. Edition Professional Communications Inc., Greenwich, CT. , 2018.

My Story With Type 1 Diabetes Banting and Best

 No one in my family had type University of Toronto, 1921 1 diabetes  I was sent home from the hospital on one shot of insulin a day (NPH/Reg)  Urine testing only  No A1c test  No pumps or pens  No insulin analogs  No CGM

Edelman SV. Taking control of your diabetes: a patient oriented book on diabetes. Fifth Edition Professional Communications Inc., Greenwich, CT. , 2018.

Serum Insulin Levels in Type 1 Diabetes Blood Glucose Levels

1000 15 LisPro Regular 270 Lispro Regular

breakfast lunch dinner breakfast lunch dinner

750 180 10

500

(mmol/l) Do in mg/dL 5 90 250

Avg A1c=6.8 *p < 0.05

0 0 22.00 3.00 7.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 22.00 3.00 7.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00

Time (h) Time (h)

Jacobs. Diabetes Care. 1997; 20:1279. Jacobs. Diabetes Care. 1997;20: 1279. Subcutaneous Insulin Has A Very Physiologic Insulin, Glucagon and Narrow Therapeutic Window Amylin Secretion Systemic  Too little insulin leads to Circulation postprandial Pancreas Hyperglycemia  Too much leads to hypoglycemia

 Very difficult to get it just Insulin right Portal Vein Amylin Beta Cell

Glucagon Alpha Edelman SV. Taking control of your diabetes: a patient oriented book on diabetes. Fifth Insulin Dose Pettus J, Edelman SV. (2013) Adjunctive Therapies. In The American Diabetes Edition Professional Communications Inc., Greenwich, CT. , 2018. Association/JDRF Type 1 Diabetes Sourcebook (319-340). VA: American Diabetes Association Cell

Inhaled Insulin (Afrezza) Faster Acting Aspart or Fiasp (addition of L-arginine and niacinamide for faster absorption)

Rapid on 2 hour PG levels in Rapid off T1D onPump therapy after a standarized meal comparing Aspart (Novolog)with • Better post meal glucose Faster Aspert values (Fiasp) • Less delayed hypoglycemia Bode et al DTT Vol 19 2017 Santos Cavaiola T, Edelman SV. Inhaled insulin: A breath of fresh air? A review of inhaled insulin. Clinical Therapeutics. 2014. 36(8)

Xeris ready-to-use liquid glucagon for treatment of severe hypoglycemia

Treatment of severe hypoglycemia – Indication Translates to a strong value as per current GEK label proposition: Could a  Auto-injector delivery Dosing • 0.5 and 1.0 mg of glucagon ◦ Ultra-compact design • Pediatric and adult populations ◦ Simple, two-step Lilly ready-to- operation • SC delivery ◦ Integrated safety use liquid • SHL “Molly” auto-injector features Drug − Auto-inject and auto-retract  Pre-filled delivery glucagon Delivery − ‘Lock-out’ safety needle preferred in some market – 1 - 2 second hold down time segments Devices (labeled at 5 seconds) help  Superior caregiver/patient • Pre-filled syringe option also experience available ◦ Reduced time to address administration unmet ◦ Increased likelihood of Storage 2 years at room temperature successful administration need? ◦ Reduced anxiety Will There Be Adjustable Sizes? What is desirable: Contextual awareness

Utilization of the sensors commonly found in today’s smartphones to tie BG to:  Location – GPS  Activity ◦ Accelerometer ◦ Gyroscope  Time – day – date Courtesy of ◦ Clock mHealthSys, Inc. ◦ Calendar

BG, blood glucose

Unmet needs – wireless sensor data Unmet needs – aggregation with multivariate automatic food recognition analytics • Wirelessly interfaced metabolic Suggested portions sensors Estimate CHO, and fat • Aggregation and multivariate Recommended dose & testing schedule analytics provide deeper insights Activity Postprandial BG prediction Weight, body fat

Blood Glucose Glucose BP

Activity HR Activity

Courtesy of mHealthSys, Inc Meals/Food Intake . Courtesy of Food intake mHealthSys, Inc. BP, blood pressure; HR, heart rate CHO, carbohydrate

Scan Your Plate With Your Smart Phone App! Basal/ or MDI Insulin Regimen Integrated system With Rapid and Long-Acting Analogs/Inhaled Or Aspart BOLUS Or Breakfast Lunch Dinner Fiasp Or Captured image Segmentation Plate detection Lispro or Inhaled Insulin Food Volume Carbs type U-100/U-300 110 ml Breaded Glargine/Detemir) Degludec Breaded 110 ml 11 g InsulinAction 80 ml Salad Rice 120 ml 16.4 g 120m Rice l Basal Salad 80 ml 2.6 g Bolus Calculator CHO estimation 3D model Recognition

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 Smartphone server side Time Mougiakakou S, et al. Diabetes Tech Ther 2015:17(Suppl. 1);A126 Abstract Adapted with permission from Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy. New York: Marcel Dekker; 2002:87-112. Nathan DM. 285 N Engl J Med 2002;347:1342-1349. Smart Pens For You MDI (Multiple Daily Injection) Folks Works On The iPhone XI I

Artificial Panreas Insulin Pumps

 Tandem t:slim G5/X2  Medtronic 630/670G/530G  OmniPod

Edelman SV. Taking control of your diabetes: a patient oriented book on diabetes. 38 Fourth Edition Professional Communications Inc., Greenwich, CT. 544 pages, 2013.

530G/630G/670G Enlite by Medtronic Dexcom G4 & G5 Platinum Continuous Glucose Monitoring Devices Currently Available In The United States How CGM and Trending Information Can Affect Our Decisions (CF/I:CHO)

Herrmann K, Frias JP, Edelman SV, Lutz K, Shan K, Chen S, Maggs D, Kolterman OG. improved measures of glycemic control and body weight in patients with type 1 diabetes mellitus undergoing continuous subcutaneous insulin infusion therapy. Postgraduate Medicine. 123(3), 2013.

G5 Dexcom Now Connects Directly to the Smart Phone and Apple Watch Smart Phone Clarity App

Mean glucose value

Standard Deviation

Time in Range

24 hour multiday profile

An Artificial Pancreas Is Coming Faster How does the Auto mode feature work? AUTOMATED BASAL INSULIN DELIVERY 670G Than We Thought Possible Auto Mode: HYBTID iLet • BigFoot • Tandem • Insulet • Medtronic ▪ 48 hours before it kicksClosed in Loop ▪ Delivers automated basal insulin Resume preset basal rate doses every 5 minutes ▪ Automated basal target = 120 mg/dL 180 Alarm – ▪ Temporary target of 150 mg/dL can impending BG No response – alarm plus hypo be used mg/dL No response – automated insulin push alarm plus insulin Alarm – to bring level below Minimize time reduction or impending threshold(glucagon off) in “Red” zones off/glucagon on if hyper Bolusing & Meals needed 70 ▪ Must enter blood glucose (BG) 50 readings and/or carbohydrate grams

Time Important to Understand what it can and cannot do  This is a basal rate modulator

 Works well overnight Glucose  Still requires meal boluses, correction bolus, and many fingersticks

 Diabetes tasks during the day are not decreased

 There are more alarms

670G Study Subject Download

D.I.Y. SYSTEM

Average glucose = 153 (eA1c = 7.5%), 1% of readings < 70 mg/dl

Old Medt. Pump

iPhone

Riley Loop Always in automode iLet: Bionic Pancreas

Current BS-Blue 2 ports for Predicted dotted line-Blue insulin and glucagon

How much insulin orange (Example 6 extra units last hour) Bars above and below baseline

Exercise targets Cut out hypos almost completely No lows at night More time in range

CGM Readings On and Off the Bionic Pancreas

Eversense “Other” Therapies for People Implantable CGM with Type 1 Diabetes (under FDA review) Symlin  (GLP-1 RA)* SGLT-2 Inhibitors* Inhaled Insulin

* approved only type 2 diabetes at the current time : First-in-Class Dual A1C and Hypoglycemia:T1D SGLT1 and SGLT2 Inhibitor  Sotagliflozin significantly reduced mean A1C compared with placebo after 29 days with no increase in hypoglycemia Change in A1C Change in number of hypoglycemic events (SMBG ≤70 mg/dL), per patient per day (PPD)

0 SGLT 1 0 SGLT 2 -0.06 -0.1 -0.1 -0.2 -0.4

-0.2 -0.3 -0.7  SGLT1 is the primary transporter -0.55 baseline (PPD) -0.4 for absorption of glucose and  SGLT2 is expressed in the -0.3 -0.5 , where it reabsorbs 90% from galactose in the GI tract -0.4 of filtered glucose -0.6

-0.5 Change

Change (%) baseline Change from -0.7

-0.6 * -0.8 Placebo Sotagliflozin Placebo Sotagliflozin Multiple events for a patient were each counted GI, gastrointestinal; SGLT, sodium-dependent glucose transporter Diabetes Care. 2015; 38(7):1181-8. *P = 0.002 relative to SMBG, self-monitoring of blood Diabetes Care. 2015; 38(7):1181-8. placebo glucose

CGM Time in Target, Hyperglycemic, Body Weight T1D and Hypoglycemic Ranges T1D

 Patients treated with sotagliflozin demonstrated weight loss Baseline Treatment compared with weight gain in the placebo group CGM CGM Days –2 to –6 Days 3–5.827 8.5 Blood glucose 1 Placebo CGM 55 54 40.2 <70 mg/dL 0.5 35. % time in 6 0.5 . 70–180 mg/dL 0 ranges >180 mg/dL -0.5 7.9 6.7 -1.7 -1 P=0.002 vs. Change from baseline (kg) Sotagliflozin 25 -1.5 68.2 placebo % time in 56.4 35.7 P=0.003 * vs. -2 placebo Placebo Sotagliflozin ranges

*P = 0.005 relative to placebo Diabetes Care. 2015; 38(7):1181-8. Diabetes Care. 2015; 38(7):1181-8.

Phase 3 Program in T1DM Summary Type 2 Diabetes Trends Among

 inTandem program has the largest efficacy and safety database of an oral Adults in the U.S. 1990 anti-diabetic agent for T1DM

 Sotagliflozin significantly: ◦ Reduced A1C ◦ Reduced body weight ◦ Reduced blood pressure ◦ Reduced bolus insulin (leading to less hypoglycemia) ◦ Glucose variability (more time in range) ◦ Reduced severe hypoglycemia in the setting of optimized insulin setting

 Benefit/risk profile favorable ◦ Additional A1C efficacy on top of insulin (consistent with SGLT 2 inhibition) ◦ Efficacy beyond A1C ◦ No increase in severe hypoglycemia, lower PPG, lower incidence of No Data Less than 4% 4% - 6% Above 6% documented hypoglycemia (consistent with SGLT1 inhibition)

◦ DKA is manageable with appropriate care instructions Mokdad et al., Diabetes Care 2000;23:1278-83. Diabetes Trends Among Adults in the U.S. You Can Get Type 1 and Type 2 2017: Over 258 billion dollars a year! Diabetes at Any Age!

LADA No Data Less than 4% 4% - 6% Above 6% Above 10% Jose diagnosed Barbara diagnosed www.diabetes.org with Type 2 at age 5 with Type 1 at age 64

Risk of Developing Type 1 And T2D The Prevalence General Population 0.3% 8-11% of Type 2 Diabetes and Diabetes Mean body weight If you have a sibling with 7.5 78 The genes 4% ~30% (%) T1D 7.0 77 for type 2 If your mother has T1D 6.5 76 2 – 3% ~30% 6.0 75 diabetes and 5.5 74

If your father has T1D 6 – 8% ~30% 5.0 obesity are Pounds 4.5 73

Body Weight kg Weight Body linked 4.0 72 If you have an identical 1990 1992 1994 1996 1998 2000

~50% 100% Prevalence inPopulation twin with T1D 1990’s 2017 together Years

Central or Abdominal Obesity of Type 2 Diabetes MRI of the Belly

White is abdominal fat Causes of Mortality in Patients With Most Common Causes of Death in People With Diabetes 20 years Ago: Type 2 Diabetes: It is not eye, kidney or nerve disease! The same Trend Exists in 2017 50 Almost 80% do to any type Pneumonia/ Other 40 Malignant Influenza of heart disease and stroke Neoplasms 4% 5% 13% % of 30 55% Deaths 13% Heart Disease 20 “Diabetes 10% complications” 10

0 Ischemic Other Diabetes Cancer Stroke Infection Other STROKE Heart Heart related Disease Disease

http://professional.diabetes.org/?loc=bb-dorg http://professional.diabetes.org/?loc=bb-dorg Geiss LS, et al. In: Diabetes in America, 2nd ed. 1995. Bethesda, MD: National Institutes Diabetes in America.. NIH No. 95-1468. 1995:233-257. of Health; 1995:Chapter 11.

J Relatively New Class of Injectable Fixed Combinations Of Basal Insulin and GLP1-RA Medications for Type 2 Diabetes Xultophy and Soliqua GLP-1 RA Trulicity

AstraZeneca NovoNordisk Lilly Improved control (A1c) WEIGHT LOSS Two excellent diabetes in one pen! “Basal that are super charged” Low risk of low blood glucose Lancet Diabetes Endocrinol. 2014 Nov;2(11):856-8, 2017 PDR PIs

ITCA 650—Medical Device To Deliver Type 2 medication  57 years of age BMI 32, drug naïve or MEDICINE: TECHNOLOGY  DOD 6.3 years  A1c Oral (-0.7 to -1.9%) Dose ranging  Previously-  Previously- approved delivery approved GLP-1  A1c Injectable semaglutide -1.9% system therapeutic with  A1cOral placebo -0.3%  Small micropump demonstrated: −Maintains stability −Glycemic control at temps ≈37⁰C −Weight loss  Weight loss oral smeaglutide -6.9kg (highest dose) −Maintains stability −Safety  Weight loss injectable semaglutide -6.4% for > 12 months

 Mild to moderate GI side effects in both groups Not yet approved by the FDA Large Non-Insulin CVOTs in T2DM Large Non-Insulin CVOTs in T2DM DPP-4 Inhibitors GLP-1 Receptor Agonists

Study SAVOR EXAMINE TECOS CAROLINA CARMELINA Study LEADER ELIXA SUSTAIN EXSCEL REWIND 6 DPP4-i saxaglip linagliptin tin✓ ✓ ✓ GLP1-RA semaglutide exenatide LR Comparator placebo placebo plcebo placebo ✓ ✓ ✓ ✓ N 16,500 5,400 14,000 6,000 8,300 Comparator placebo placebo placebo placebo placebo Results 2013 2013 June 2017 2017 N 16,500 14,000 6,000 5,400 8,300 2015 Results 2016 2015 2016 2018 2019

Courtesy of Silvio Inzucchi MD, Yale University

Large Non-Insulin CVOTs in T2DM Investigatte Before Vilifying A Medication SGLT-2 Inhibitors (relative risk vs absolute risk) (imbalance that is statistically significant)

Study EMPA-REG CANVAS DECLARE NCT01986  881 Avandia (): CAD  Actos (): bladder cancer SGLT-2-i empaglifozin✓ ✓ (Lantus): breast cancer Comparator placebo placebo placebo placebo  DPP-4 inhibitors: pancreatic cancerElvis N 7300 4300 22,200 3900  Onglyza (): hosp. for CHF Results Sept 2015 2017 2019 2020  Invokana (canagliflozin): amputation  Ozempic (semaglutide) retinopathy/DME

Courtesy of Silvio Inzucchi MD, Yale University

Abbott FreeStyle Libre: Future Developments Now approved in the US

Waterproof Lasts 10 days 12 hour warm up Swipe to get a number Develop: No calibration • A simple Low Cost • Easy to apply • Low cost • Disposable sensor Will give you a swipe • Integrated into a glucose reading monitor or smart phoneevery 5 minutes! Natural History of Type 2 Diabetes Is Characterized by Progressive Loss of Beta Cell Function Completed diabetes prevention trials Progression of Dysglycemia Relative risk Clinical study Treatment (3-4 years) Type 2 Diabetes reduction

Insulin resistance Finnish Diabetes Prevention Study Diet & exercise vs. control 58%

Diet & exercise vs. 58% Diabetes Prevention Program placebo Insulin secretion 31% Metformin vs placebo Prediabetes and Early Type Postprandial glucose 2 Diabetes: Generally STOP-NIDDM vs. placebo 25% Asymptomatic Fasting glucose Tripod in GDM 56%

XENDOS Orlistat vs. placebo 45% Microvascular complications Macrovascular complications DREAM Rosiglitazone vs. placebo 62% Years to Decades Progression to Type 2 Diabetes Diagnosis of Type 2 ACT NOW Pioglitazone vs. placebo 72% Can be Prevented or Delayed Diabetes Typically Delayed Insulin glargine vs. ORIGIN 28% placebo Adapted from Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789 Edelman, S. Diagnosis and Management of Type 2 Diabetes 10th Edition, Chapter 16.

ONLY ABOUT HALF OF PATIENTS ACHIEVE Developments In The Past HbA1c <7% WITH VIRTUALLY NO CHANGE OVER THE LAST DECADE

Decade For Type 2 Diabetes 100

90 NNO CHANGE IN THE LAST DECADE 80  DPP4 inhibitors (4 in the class) 70

 SGLT2 Inhibitors (3 in the class) 60 56.8% 52.2% 50.9%  GLP1-RA (5 in the class) 50

Achieving HbA1c <7% HbA1c Achieving 40  Several positive CVOT trials a 30  Newer basal insulins

20 Patients

 Fixed combinations of GLP1-RA & basal insulins 10 % of %  Insulin pumps for type 2 (Vgo and the T-Flex) 0 2003-20061 2007-20101,2 2011-20142  Inhaled insulin N=999 N=1444 N=2677 NHANES Data  Software programs and multiple apps NHANES, National Health and Nutrition Examination Survey. aPatients with either Type 1 or Type 2 diabetes. 1. Ali MK et al. N Engl J Med. 2013;368:1613-1624. 2. Carls GS et al. 76th ADA Scientific Sessions. June 10–14, 2016. Poster 1515-P.

COMMERCIAL HMO AND MEDICAID RATES OF VERY POOR GLYCEMIC CONTROL IN POPULATION RESULTS ARE EVEN WORSE DIABETES HAVE ALSO NOT IMPROVED

HEDIS data from >1000 health plans covering >171 million lives in 2014 HEDIS data from >1000 health plans covering >171 million lives (2014)

ONLY ABOUT 40% OF PATIENTSa ONLY ABOUT 30% OF PATIENTSa ARE AT HbA1c <7% ARE AT HbA1c <7%

100 100 2005 2014 HMO POPULATION % OF DIABETIC 90 90 MEDICAID POPULATION 80 80 PATIENTS WITH 70 70 VERY POOR GLYCEMIC NO CHANGE IN 10 YEARS NO CHANGE IN 10 YEARS 60 60 CONTROL 29.7% 31.1% 50 50 OF ALL OF ALL 40 40 (HbA1c >9%) PATIENTS PATIENTS 30 30 IN THE US WITH WITH 20 20 DIABETES* DIABETES* 10 10

0 0

% of Patients Achieving HbA1c <7% HbA1c Achieving Patients of % % of Patients Achieving HbA1c <7% HbA1c Achieving Patients of % 2007 2008 2009 2010 2011 2012 2013 2014 2007 2008 2009 2010 2011 2012 2013 2014

HEDIS, Healthcare Effectiveness Data and Information Set. aPatients with either Type 1 or Type 2 diabetes. *In a commercial HMO population that includes either Type 1 or Type 2 diabetes. National Committee for Quality Assurance. http://www.ncqa.org/ReportCards/HealthPlans/StateofHealthCareQuality.aspx. National Committee for Quality Assurance. http://www.ncqa.org/ReportCards/HealthPlans/StateofHealthCareQuality.aspx. INCREASING INCREASING THE US IN MEDICAL COSTS OF T2DARE $100 $150 $200 $250 $300 $350 $400 from drug initiation to 365 characteristics. a RCT, randomized . Carls Carls GS et 76thal. ADAScientific Sessions. June 10 $50 Total Linear $0 RAs CONTRIBUTORTO THE EFFICACYGLP GAP: KEY THE IS ADHERENCE POOR Reference: Reference: regression model fitted to estimate the change in HbA1c 1 year after initiating GLP * Includes medical * medical Includes coststype of diabetes2 related andcomplications. 2007 UnitedHealth UnitedHealth Group, TheUnited States ofDiabetes: Challenges and opportunities in the decade ahead. Working paper 5. Novembe

b $110 Optum US Medical Costs for Diabetes From From Diabetes for Costs Medical US US in person every for burden cost >$1000 2008 / Humedica

± $119 90 days later

Change in HbA1c (%) PREDICTED UNDER TYPICAL 2009 REAL – – – – – – – – SmartFile database (2007 0.8 0.6 0.4 0.2 1.6 1.4 1.2 1.0 TRIAL 2020 (in billion billion (in 2020

0 $130 . - c WORLDRESULTS Medical Medical adherence classified aspoorly adherent if percentage of days covered (PDC)<80%. 2010 CONDITIONS - 1.04% $140 2011 – 14, 14, 2016. New Orleans, LA. Poster 117 $151 - 2014) was used (GLP a 2012 GAP GAP

WORLD $164 - 0.52% REAL 2013 b { $180 - 1 RA221 patients; DPP US 2014 EXPLAINING -

1 RAor DPP $202 THE THE GAP 25% 75% dollars)* 2015 - LB. $224 - 4i based on baseline and treatm - 4i 652 patients). Change in HbA1cmeasured 2016 THERAPY ADDITIONAL DRUG CHARACTERISTICS, BASELINE ADHERENCE $249 2017 $274 c 2018

r 2 r $301 010. 2007 to to 2007 ent 2019 $331 - 1 2020 $363 Get Type 2 (TCOYD) Director,Taking Controlof YourDiabetes University ClinicalProfessorofMedicine V.Steven Edelman, DISEASE INEXPENSIVE NOT IS AN IT AND DISEASE RARE NOT A IS DIABETES Type Diabetes CareDiabetes for (acceptedpublication) Disappear In RealIn World Disappear of California,of San Video 2 longertype liveof Diabetes..And Clinical TrialClinical Results 2 Diabetes: 2 Diabetes: Diego MD Live LongerIt! BecauseOf UniversityCalifornia,of SanDiego President,g William ClinicalProfessorofMedicine Practice? Behaviorall Why Do Do Why Polonsky DiabetesInstitute(BDI)) $ PhD THANK YOU! [email protected] Steven V. Edelman, MD Professor of Medicine University of California San Diego School of Medicine Veterans Affairs Medical Center Founder and Director, Taking Control Of Your Diabetes, a 501(c)3 Not-for-Profit Organization