986-P: Efficacy of Semaglutide by Background Sodium-Glucose Cotransporter 2 Inhibitor: A Post Hoc Analysis of SUSTAIN 9

Abstract

The SUSTAIN clinical trials demonstrated the efficacy and safety of once-weekly subcutaneous semaglutide, a glucagon-like peptide 1 analog for the treatment of type 2 diabetes (T2D). SUSTAIN 9 investigated semaglutide 1.0 mg vs. placebo as add-on to a stable dose of sodium-glucose co transporter-2 inhibitor (SGLT2i) therapy, with or without metformin or a sulfonylurea. The primary and secondary endpoints were, respectively, change from baseline in HbA1c and body weight at week 30. In this post hoc analysis, SUSTAIN 9 data were analyzed by background SGLT2i (empagliflozin, canagliflozin, dapagliflozin or other [ipragliflozin, luseogliflozin and tofogliflozin; drugs available only in Japan]). In total, 302 subjects were randomized to semaglutide or placebo. Reductions in HbA1c and body weight were greater with semaglutide vs. placebo. There was no significant interaction between background SGLT2i and treatment effect (interaction p-value >0.05 for both endpoints), with a smaller observed weight reduction in the ‘Other’ group (Table). No safety concerns were identified when adding semaglutide to SGLT2i therapy. No diabetic ketoacidosis or lower limb amputation events occurred. In conclusion, in subjects with T2D already receiving an SGLT2i, semaglutide generally resulted in superior HbA1c and body weight reductions vs. placebo, regardless of background SGLT2i therapy. Disclosure B. Zinman: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. Consultant; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. V. Bhosekar: None. R.S. Busch: Advisory Panel; Self; Janssen Pharmaceuticals, Inc. Research Support; Self; Bayer AG. Speaker's Bureau; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi US. Stock/Shareholder; Self; Amarin Corporation. I. Holst: Employee; Self; Novo Nordisk A/S. B. Ludvik: Advisory Panel; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Sanofi, Takeda Development Centre Europe Ltd. Research Support; Self; Akebia Therapeutics, Eli Lilly and Company, Novartis AG, Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp. J. Thrasher: Advisory Panel; Self; Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi, Senseonics. Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Sanofi. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc. V.C. Woo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. A. Philis-Tsimikas: Advisory Panel; Self; AstraZeneca, Lilly Diabetes, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Dexcom, Inc., Glooko, Inc., National Institute of Diabetes and Digestive and Kidney Diseases. Stock/Shareholder; Spouse/Partner; Ionis Pharmaceuticals, Inc., Novo Nordisk Inc. Funding Novo Nordisk A/S