Sotagliflozin (SOTA), a dual SGLT1 and SGLT2 inhibitor, is indicated to reduce the risk of CV death and hospitalization for heart failure (HF) in adults with HF or type 2 diabetes (T2D), chronic kidney disease and other CV risk factors. SOTA has previously demonstrated glycemic efficacy as an adjunct to insulin therapy in patients with type 1 diabetes (InTandem program). This study assessed the safety and efficacy of SOTA in T2D participants with inadequate glycemic control on basal insulin with up to two glucose-lowering oral agents. This was a Phase 3, multicenter, double-blind, placebo (PBO)-controlled, parallel-group study that enrolled 570 T2D participants (baseline mean HbA1c 8.45%, age 62.4 yrs, T2D duration 14.8 yrs, BMI 32.4 kg/m2, basal insulin dose 51 IU), who were randomized 2:1:1 to once daily SOTA 400 mg, SOTA 200 mg, or PBO. Primary objective was superiority of SOTA 400 mg vs. PBO in HbA1c reduction following an 18-week core treatment period conducted without insulin adjustments. Subsequently, a 52-week extension period, allowed for insulin adjustment based on target FPGs. Adverse events were assessed over the 52-week period. At Week 18, SOTA 400 mg had a PBO-subtracted least squares (LS) mean HbA1c reduction of -0.55% (p<0.0001). At week 52, the LS mean change in A1c from baseline was -0.57% in the SOTA 400 mg group and 0% with PBO (p=0.074). Week 18 and Week 52 LS mean differences in HbA1c for SOTA 200 mg vs, PBO were -0.45% (p<0.0001), and -0.52% (p=0.13), respectively. Overall incidence of adverse events was comparable in all groups. Incidence of Level 2 hypoglycemia (<54 mg/dL) were 17%, 22% and 21% for PBO and SOTA 200 and 400 mg, respectively, and there was only 1 episode of DKA with SOTA 400 mg.
In conclusion, SOTA 400 mg once day significantly improved HbA1c in T2D with inadequate glycemic control on basal insulin therapy with a slight increase in non-severe hypoglycemia.
J. Rosenstock: Research Support; Biomea Fusion, Inc. Other Relationship; Lilly Diabetes. Research Support; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Corcept Therapeutics. Other Relationship; Novo Nordisk. Research Support; Pfizer Inc. Other Relationship; Sanofi, Boehringer-Ingelheim. Research Support; Shionogi & Co., Ltd. Other Relationship; Structure Therapeutics, Inc. Advisory Panel; Terns Pharmaceuticals, Zealand Pharma A/S. Other Relationship; Applied Therapeutics, Hanmi Pharm. Co., Ltd., Oramed Pharmaceuticals. Advisory Panel; Scholar Rock. A.K. Carroll: Employee; Lexicon Pharmaceuticals, Inc. M.B. Hardin: Employee; Lexicon Pharmaceuticals, Inc. P.L. Banks: Employee; Lexicon Pharmaceuticals, Inc. J.B. Buse: Other Relationship; Novo Nordisk. Consultant; Corcept Therapeutics. Research Support; Corcept Therapeutics, Dexcom, Inc., Insulet Corporation. Consultant; Alkahest, Anji Pharmaceuticals, Aqua Medical, Altimmune Inc., AstraZeneca, Boehringer-Ingelheim, CeQur, Eli Lilly and Company, embecta, GentiBio, Glyscend Inc., Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, LLC, Stability Health, Terns Pharmaceuticals, Insulet Corporation, Vertex Pharmaceuticals Incorporated, vTv Therapeutics. Other Relationship; Medtronic. Stock/Shareholder; Glyscend Inc., Mellitus Health, Pendulum Therapeutics, Praetego, LLC, Stability Health. M.J. Davies: Other Relationship; AstraZeneca, Boehringer-Ingelheim, Novo Nordisk, Sanofi-Aventis U.S., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Pfizer Inc., ShouTi Pharma Inc., Medtronic, Eli Lilly and Company, Napp Pharmaceuticals Limited, Novartis AG, Amgen Inc. H.S. Bajaj: Research Support; Abbott, Amgen Inc., Anji Pharmaceuticals, Boehringer-Ingelheim, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc. A.L. Peters: Advisory Panel; Lilly Diabetes, Vertex Pharmaceuticals Incorporated, Medscape. Research Support; Abbott, Insulet Corporation.
Lexicon Pharmaceuticals, Inc., The Woodlands, TX, USA
