Clinical trials (inTandem, SOLOIST-WHF, and SCORED) utilizing sotagliflozin (SOTA), a dual SGLT1 and SGLT2 inhibitor, have demonstrated glycemic improvements in patients with type 1 diabetes (T1D) and reduced heart failure-related hospitalizations and cardiovascular mortality in patients with type 2 diabetes (T2D). The purpose of this study was to evaluate the superiority of SOTA vs placebo and noninferiority of SOTA vs empagliflozin (EMPA), a selective SGLT2 inhibitor, on HbA1c reduction in individuals with T2D who had inadequate glycemic control on a DPP4i with or without metformin. This phase 3, double-blind, placebo- and active-control, parallel-group 26-week trial randomized 770 participants (mean HbA1c 8.2%, age 59.4 yrs, T2D duration 9.2 yrs, BMI 32.2 kg/m2) to receive SOTA 400 mg once daily, EMPA 25 mg once daily, or matching placebos. Changes in HbA1c, postprandial glucose (PPG), fasting plasma glucose (FPG), body weight, and systolic blood pressure (SBP) were assessed, as well as adverse events. SOTA was superior to placebo and noninferior to EMPA in reducing HbA1c. Additionally, SOTA was superior to placebo for other metabolic measurements. Percentage of patients with at least 1 hypoglycemic event, Levels 1 - 3 included, was 4.5% in the placebo group, 0.7% in the SOTA group, and 2.9% in the EMPA group. Other adverse events in the SOTA group aligned with expectations associated with SGLTi therapy.

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Disclosure

A.L. Peters: Advisory Panel; Lilly Diabetes, Vertex Pharmaceuticals Incorporated, Medscape. Research Support; Abbott, Insulet Corporation. M.B. Hardin: Employee; Lexicon Pharmaceuticals, Inc. A.K. Carroll: Employee; Lexicon Pharmaceuticals, Inc. P.L. Banks: Employee; Lexicon Pharmaceuticals, Inc. 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.

Funding

Lexicon Pharmaceuticals, Inc.

© 2024 by the American Diabetes Association
2024
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