Late Breaking Abstracts July 2018 | Volume 67 | Suppl. 1A | www.diabetes.org/diabetes Late Breaking Abstracts LB1-LB83 Subject Index LB84-LB85 Abstract Author Index LB86-LB94 Abstract Author Disclosure Information LB95-LB109 www.scientificsessions.diabetes.org EVOLVING CONCEPTS IN CLINICAL MANAGEMENT STRATEGIES Moderated Poster Discussion: Evolving Concepts in Clinical Manage- Table. ment Strategies (Posters 1-LB to 6-LB) & 1‑LB NGM282 Significantly Reduces Hepatic Steatosis Independent of 2 Diabetes (T2D) Status or Statin Usage—Results from a Phase 2 Trial in Patients with Nonalcoholic Steatohepatitis (NASH) ALEX DEPAOLI, STEPHEN J. ROSSI, LEI LING, STEPHEN A. HARRISON, MANAL F. POSTERS Complications ABDELMALEK, MARK R. JAROS, RANSI SOMARATNE, South San Francisco, CA, DISCUSSION Live Oak, TX, Durham, NC, Denver, CO Acute and Chronic Background: NGM282 is an engineered variant of human FGF-19 that retains POSTER MODERATED bile acid and metabolic regulatory activities while eliminating the tumori- genic effects of FGF-19. Multiple preclinical models showed improvements in NASH liver histology similar to those observed post-bariatric surgery. Data from a Phase 2 trial in NASH patients showed significant reductions in hepatic steatosis, liver transaminases and markers of fibrosis that were translated to histologic benefits in NASH. Both T2D status and statin ther- apy have been variably associated with treatment response in NASH trials. This analysis assessed NGM282 impact on liver fat content by T2D status and statin usage. Methods: Patients with biopsy-confirmed NASH (n=82) were randomized to NGM282 3 or 6mg or placebo for 12 weeks. The primary endpoint was & 3‑LB ≥5% reduction in absolute liver fat content (LFC) by MRI-PDFF. Patients were Liraglutide as an Additional Treatment to Insulin in Patients with stratified by T2D status at baseline and categorized as statin/no statin use Type 1 Diabetes Mellitus—A 52‑Week Randomized Double‑Blinded (3 months prior to screening). Statin therapy was stable during the study. Placebo‑Controlled Clinical Trial Treatment responses were analyzed using an ANCOVA model; NGM282 PARESH DANDONA, HUSAM GHANIM, NITESH D. KUHADIYA, TANVI SHAH, treatment arms were pooled (n=53). JEANNE M. HEJNA, ANTOINE MAKDISSI, MANAV BATRA, AJAY CHAUDHURI, Results: T2D and statin use was present in 62% and 45% of the NGM282 Williamsville, NY, Buffalo, NY, Reno, NV treated patients, respectively. There was no significant difference in LFC We have previously demonstrated that a 12-week addition of liraglutide to reduction in patients with T2D vs. no T2D (-10.4% vs.-11.2%, p=0.59) or statin insulin therapy in patients with type 1 diabetes (T1D) results in an improve- use vs. no statin use (-10.7% vs. -10.7%, p=0.99) at baseline. Absolute LFC ment in glycemic control, weight loss and a reduction in systolic blood pres- was decreased by -9.7% and -11.9% for NGM 282 3 and 6mg (p<0.001 for sure (SBP). We have now conducted a 1 year randomized study investigating both), respectively. Reductions in LFC correlated with improvements in C4, effects of liraglutide in patients with T1DM. All patients had T1D for at least HbA1c and triglycerides. one year, were on insulin therapy and had no detectable c-peptide in plasma Conclusions: NGM282 is highly effective in reducing LFC, independent (mean BMI: 28.9±1.4kg/m2, mean HbA1c: 7.82±0.16%, mean age: 46.7±1.9 of T2D status or statin use. These data support the activity of NGM282 in years, mean age of T1D diagnosis: 22.3±1.7 years). They were randomized to NASH across a broad patient population. Ongoing studies will evaluate the receive placebo, (n=20) or 1.8mg Liraglutide (n= 26) daily for 52 weeks. Con- translation of these effects into improvements in fibrosis and resolution of tinues glucose monitoring (CGM) was performed for 4 weeks before and at NASH. end of treatment. At the end of 52 weeks treatment with liraglutide, placebo adjusted HbA1c fell significantly by 0.57±0.17% (p=0.006 vs. placebo) from & 2‑LB 7.920.15± to 7.45±0.12% (p=0.009). Weekly placebo adjusted average blood Effect and Safety of Oral Semaglutide Monotherapy in Type 2 Diabe‑ glucose fell by 15±4mg/dl (p=0.014 vs. placebo) from 174±5 to 156±6mg/dl tes—PIONEER 1 Trial (p=0.021) and fasting weekly glucose fell by 8±7mg/dl (p=0.075 vs. placebo) VANITA R. ARODA, JULIO ROSENSTOCK, YASUO TERAUCHI, OLE JEPPESEN, ERIK from 165±7 to 153±9mg/dl (p=0.032). There was no change in reported inci- CHRISTIANSEN, CHRISTIN L. HERTZ, MARTIN HALUZIK, Boston, MA, Dallas, TX, dences of hypoglycemia and no change in percent time spent below 70mg/ Yokohama, Japan, Søborg, Denmark, Bagsvaerd, Denmark, Prague, Czech Republic dl based on CGM. Total insulin dose did not alter. There was a significant Oral semaglutide (sema), the first GLP-1 receptor agonist in a tablet formu- weight loss by 2.5±0.9kg (placebo adjusted, p=0.041 vs. placebo) from lation, is in late-stage development for the treatment of T2D. The effect and 83.6±4.1 to 80.5±4.0kg (p=0.01) in the liraglutide group. Placebo corrected safety of oral sema (3, 7, or 14 mg once daily) was assessed in this random- SBP also fell following liraglutide treatment by 9±3mmHg (p=0.031) from ized, double-blind, placebo-controlled phase 3a trial in drug-naïve patients 128±3 to 122±3 mmHg while placebo adjusted diastolic BP fell by 5±1mmHg with T2D uncontrolled on diet and exercise (n=703). Primary endpoint was from (79±2 to 75±2mmHg). We conclude that the addition of liraglutide to insulin treatment in type 1 diabetes significantly reduced HbA1c, mean and change from baseline in HbA1c at week 26. The primary estimand (treatment policy) evaluated the effect regardless of trial product discontinuation or fasting blood glucose, blood pressure and body weight without significant rescue medication use (effectiveness). A secondary estimand (hypothetical) increase in hypoglycemia. evaluated the effect of trial product while on treatment without rescue med- Supported By: National Institutes of Health/National Institute of Diabetes and ication (efficacy) using a mixed model for repeated measures (MMRM), and Digestive and Kidney Diseases is the method used in many previous T2D studies. Oral sema resulted in clini- cally meaningful reductions in both HbA (all doses) and body weight (higher 4‑LB 1c & doses) at week 26 (Table). Adverse events (AEs) occurred in 58, 53 and 57% Canagliflozin (CANA) vs. Other Antihyperglycemic Agents on the for 3, 7 and 14 mg oral sema, respectively, and 56% with placebo. The most Risk of Below‑Knee Amputation (BKA) for Patients with T2DM—A common AE with oral sema was transient mild or moderate nausea. Nausea Real‑World Analysis of >700,000 U.S. Patients occurred in 5-16% of patients with oral sema vs. 6% with placebo. Oral sema PATRICK RYAN, JOHN B. BUSE, MARTIJN SCHUEMIE, FRANK DEFALCO, ZHONG demonstrated superiority vs. placebo in reducing HbA1c (all dose levels) and YUAN, PAUL STANG, JESSE A. BERLIN, NORM ROSENTHAL, Raritan, NJ, Chapel body weight (14 mg) and was well tolerated in T2D uncontrolled on diet and Hill, NC exercise (ClinicalTrials.gov NCT02906930). Sodium glucose co-transporter 2 inhibitors (SGLT2i) are indicated for treat- ment of T2DM; some SGLT2i have reported a CV benefit and some reported a risk of BKA. U.S. claims databases were analyzed using a prespecified protocol to examine CANA-associated effects on BKA and hospitalization for heart failure (HHF) vs. other SGLT2i and non-SGLT2i. Analyses used a pro- pensity score adjusted new user design with numerous sensitivity analyses. The 4 databases included 142K new users of CANA, 110K of other SGLT2i, and 460K of non-SGLT2i AHAs. Meta-analysis results are reported when heterogeneity across databases was not substantial (I2 <0.4). There was no evidence of increased risk of BKA with CANA vs. non-SGLT2i or other SGLT2i in on-treatment or ITT analyses (Table). HHF benefits were demonstrated in ADA-Supported Research LB1 EVOLVING CONCEPTS IN CLINICAL MANAGEMENT STRATEGIES these analyses, consistent with clinical trials. Similar BKA and HHF results Insulin Change from Baseline at Week 52 were seen in a subgroup with established CV disease. In this large compre- Total insulin hensive analysis, neither CANA nor other SGLT2i showed an increased risk ‑ Percent change (%) from Baseline of amputation vs. non-SGLT2i. Because on-treatment median exposure was LS Mean (SE), p-value 2.12 (0.959), p=0.028 -4.98 (0.955), p<0.001 -8.21 (0.958), p<0.001 <6 months, future observational studies with longer duration are needed. Treatment Comparison vs. Placebo LS Mean (SE), p-value N/A -7.10 (1.301), p<0.001 -10.33 (1.303), p<0.001 This study helps to further characterize the potential benefits and harms of ‑ Absolute change (IU) SGLT2i as observed in routine clinical practice to complement the evidence LS Mean (SE), p-value 0.18 (0.657), p=0.78 -3.51 (0.654), p<0.001 -5.86 (0.656), p<0.001 from clinical trials and prior observational studies. Bolus insulin ‑ Percent change (%) from Baseline DISCUSSION LS Mean (SE), p-value 5.14 (2.338), p=0.028 -1.48 (2.332), p=0.52 -8.58 (2.338), p<0.001 Treatment Comparison vs. placebo LS Mean (SE), p-value N/A -6.63 (3.182), p=0.037 -13.73 (3.187), p<0.001 MODERATED POSTER MODERATED ‑ Absolute change (IU) LS Mean (SE), p-value -1.45 (0.511), p=0.004 -3.08 (0.508), p<0.001 -4.28 (0.510), p<0.001 ‑ Proportion of insulin reduction attributable to bolus insulinb N/A 82.8% 71.3% Basal insulin ‑ Percent change (%) from Baseline LS Mean (SE), p-value 4.75 (1.137), p<0.001 -2.36 (1.136), p=0.038 -4.50 (1.136), p<0.001 Treatment Comparison vs.