Sotagliflozin Research Articles

Fifty-Two-Week Efficacy and Safety of Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Adults with Type 1 Diabetes (The European inTandem2 Study)

Sotagliflozin (SOTA) is a dual SGLT1 and SGLT2 inhibitor in development as adjunct therapy to insulin in T1D. In this double-blind, 52-week study, 782 adults with T1D treated with multiple daily insulin injections or pump therapy were randomized 1:1:1 to placebo (n=258), SOTA 200 mg (n=261) or SOTA 400 mg (n=263) once daily after 6 weeks of insulin optimization. Primary endpoint was change from baseline in A1C at Week 24. Other endpoints included A1C, documented hypoglycemia (DH), weight and FPG change at Week 52, patient (pt) reported outcomes (PROs) and net clinical benefit (NCB), assessing the proportion of pts with A1C Baseline characteristics were similar between groups. Compared with placebo, treatment with SOTA 200 or 400 mg improved A1C and pt satisfaction at Week 24 and reduced A1C, DH rate, weight, FPG and pt distress at Week 52 (Table). More pts achieved NCB in the SOTA arms vs. placebo (Table). Pts receiving SOTA 400 mg had the least SH events, but more genital mycotic infections, DKA and diarrhea than placebo. In conclusion, SOTA 200 and 400 mg were associated with statistically significant A1C reductions that were sustained (P Disclosure T. Danne: Speaker9s Bureau; Self; A. Menarini Diagnostics. Advisory Panel; Self; Abbott, AstraZeneca, Bayer AG, Boehringer Ingelheim GmbH. Speaker9s Bureau; Self; Dexcom, Inc.. Research Support; Self; Eli Lilly and Company. Stock/Shareholder; Self; DreaMed Diabetes, Ltd.. Research Support; Self; Insulet Corporation. Speaker9s Bureau; Self; Menarini Group. B. Cariou: Board Member; Self; Amgen Inc.. Consultant; Self; Genfit. Board Member; Self; Novo Nordisk A/S. Speaker9s Bureau; Self; Merck Sharp & Dohme Corp.. Board Member; Self; Sanofi-Aventis, Regeneron Pharmaceuticals, Inc. P.L. Banks: Employee; Self; Lexicon Pharmaceuticals, Inc. M. Brandle: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp.. Research Support; Self; Novo Nordisk Foundation. Speaker9s Bureau; Self; Novartis Pharmaceuticals Corporation. H. Brath: Speaker9s Bureau; Self; Abbott. Advisory Panel; Self; Amgen Inc.. Speaker9s Bureau; Self; Amgen Inc.. Advisory Panel; Self; AstraZeneca. Speaker9s Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker9s Bureau; Self; Boehringer Ingelheim GmbH, Eli Lilly and Company, Medtronic. Advisory Panel; Self; Merck Sharp & Dohme Corp.. Speaker9s Bureau; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Novartis AG. Speaker9s Bureau; Self; Novartis AG. Advisory Panel; Self; Novo Nordisk Inc.. Speaker9s Bureau; Self; Novo Nordisk Inc., Pfizer Inc.. Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH. Speaker9s Bureau; Self; Sanofi-Aventis Deutschland GmbH. Board Member; Self; Austrian Diabetes Association. E. Franek: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker9s Bureau; Self; AstraZeneca, Bristol-Myers Squibb Company, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Servier. J.A. Kushner: Advisory Panel; Self; Lexicon Pharmaceuticals, Inc.. Consultant; Self; KNOW Foods, Inc. P. Lapuerta: Employee; Self; Lexicon Pharmaceuticals, Inc.. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc., Merck & Co., Inc. D.K. McGuire: Consultant; Self; AstraZeneca, Sanofi-Aventis, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi-Aventis, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Lexicon Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Esperion Therapeutics. A.L. Peters: Advisory Panel; Self; Abbott, Bigfoot Biomedical. Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Eli Lilly and Company, Insulin Algorithms, JDRF, Lexicon Pharmaceuticals, Inc., Livongo Health. Research Support; Self; MannKind Corporation. Other Relationship; Self; Medscape. Advisory Panel; Self; Merck & Co., Inc.. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Speaker9s Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Omada Health, Inc., Optum Rx, Inc., Sanofi. Research Support; Self; T1D Exchange. Advisory Panel; Self; The Endocrine Society. Research Support; Self; The Leona M. and Harry B. Helmsley Charitable Trust. Advisory Panel; Spouse/Partner; Johnson & Johnson Diabetes Institute, LLC. S. Sawhney: Employee; Self; Lexicon Pharmaceuticals, Inc.. Stock/Shareholder; Spouse/Partner; GlaxoSmithKline plc., AstraZeneca, Pfizer Inc., Eli Lilly and Company, Novartis Pharmaceuticals Corporation. P. Strumph: Employee; Self; Lexicon Pharmaceuticals, Inc.. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc.. Board Member; Self; College Diabetes Network.

Sotagliflozin in Combination with Optimized Insulin Therapy Reduced HbA1c Levels with a Decreased Daily Insulin Requirement after 52 Weeks in Adults with T1D

In most patients with T1D, adequate glycemic control is not achieved with insulin therapy alone, and intensifying insulin therapy can increase the risk of hypoglycemia. Sotagliflozin (SOTA) is a dual SGLT1 and SGLT2 inhibitor, which blunts and delays postprandial hyperglycemia and reduces renal glucose reabsorption. In two 52 weeks phase 3 studies adults with T1D were randomized 1:1:1 to placebo + insulin (PBO), SOTA 200 mg + insulin or SOTA 400 mg + insulin, once daily, after 6 weeks of insulin therapy optimization. HbA1c change over 52 weeks, along with change of daily insulin dose and safety, were assessed using a pooled analysis. Significant HbA1c reductions were observed with SOTA 200 or 400 vs. PBO at week 24 and sustained to 52 weeks, with a concomitant decrease in total daily insulin dose, mainly due to reduction in bolus insulin (BI), as 70-80% of the total insulin reduction was from BI for both SOTA doses. At 52 weeks, patients in SOTA groups had a lower incidence of severe hypo (SH) but more genital mycotic infections, DKA and diarrhea than PBO. In conclusion, SOTA demonstrated additional and sustained reduction of HbA1c on top of optimized insulin while reducing total daily insulin dose (mainly BI doses), with less incidence of SH. This may be an additional therapy for patients with T1D without good glycemic control despite optimized insulin therapy. Disclosure J. Pettus: Advisory Panel; Self; Sanofi, Novo Nordisk Inc.. Consultant; Self; MannKind Corporation. Advisory Panel; Self; Insulet Corporation. Consultant; Self; Senseonics. S.A. Weinzimer: Speaker9s Bureau; Self; Medtronic MiniMed, Inc., Insulet Corporation. Consultant; Self; Sanofi. Stock/Shareholder; Self; InsuLine Medical Ltd. R.J. Mccrimmon: Advisory Panel; Self; Novo Nordisk Foundation, Sanofi-Aventis. Research Support; Self; The Leona M. and Harry B. Helmsley Charitable Trust, Diabetes UK. Other Relationship; Self; Elsevier. F. Ampudia Blasco: Advisory Panel; Self; Abbott, Eli Lilly and Company, GlaxoSmithKline plc., LifeScan, Inc., Medtronic, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis. J.A. Stewart: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. P. Strumph: Employee; Self; Lexicon Pharmaceuticals, Inc.. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc.. Board Member; Self; College Diabetes Network. J.H. Oliveira: Employee; Self; Sanofi RD Spouse/Partner; Eli Lilly and Company. P. Lapuerta: Employee; Self; Lexicon Pharmaceuticals, Inc.. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc., Merck & Co., Inc. R. Castro: Employee; Self; Sanofi US.

Fifty-Two-Week Efficacy and Safety of Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Adults with Type 1 Diabetes (inTandem1)

Fifty-Two-Week Efficacy and Safety of Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Adults with Type 1 Diabetes (inTandem1)