1212-P: Sotagliflozin Reduces Markers of Arterial Stiffness in T1D: Pooled Analysis from inTandem 1 and inTandem 2 Clinical Trials

Abstract

Cardiovascular (CV) disease is a major cause of mortality in type 1 diabetes (T1D). Elevated blood pressure, including both systolic blood pressure (SBP) and diastolic blood pressure (DBP), and increased arterial stiffness are linked to CV events. While SGLT2 inhibitors have shown positive outcomes pertaining to BP and markers of arterial stiffness and vascular resistance in adults with type 2 diabetes, such effects have not been reported previously in T1D. When added as an adjunct to insulin therapy, sotagliflozin (SOTA), a dual SGLT1 and SGLT2 inhibitor, has previously demonstrated significant SBP reduction vs. placebo in adults with T1D. In this post hoc analysis, several indirect markers of arterial stiffness including pulse pressure (PP), mean arterial pressure (MAP), and double product (DP), were calculated using observed SBP, DBP or pulse rate at 24 weeks using pooled data (n=1,575) from the inTandem 1 and 2 studies. Baseline characteristics were similar among groups. Significant placebo-adjusted reductions were observed at week 24 for SOTA 200 and 400 mg in SBP, DBP, MAP, and DP, and in PP for SOTA 400 mg [Table]. The reductions in BP were not associated with increases in heart rate. In conclusion, treatment with SOTA in adults with T1D resulted in significant reduction in BP and several markers of arterial stiffness and vascular resistance. Disclosure H.W. Rodbard: Advisory Panel; Self; Bayer US, Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Spouse/Partner; Eli Lilly and Company. Consultant; Self; Gan & Lee Pharmaceuticals. Research Support; Self; Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; Merck & Co., Inc., Novo Nordisk Inc. A. Giaccari: Advisory Panel; Self; Sanofi. Board Member; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Merck Sharp & Dohme Corp., Sanofi. M.J. Davies: Employee; Self; Lexicon Pharmaceuticals, Inc. S. Sawhney: Stock/Shareholder; Spouse/Partner; AstraZeneca, Gilead Sciences, Inc., GlaxoSmithKline plc., Merck & Co., Inc., Pfizer Inc. S. Wang: Employee; Self; Sanofi US. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. B. Cariou: Board Member; Self; Novo Nordisk A/S, Regeneron Pharmaceuticals. Consultant; Self; GENFIT, Sanofi-Aventis. Research Support; Self; Amgen Inc., Pfizer Inc. Speaker's Bureau; Self; Abbott, Akcea Therapeutics, Merck Sharp & Dohme Corp. Funding Lexicon Pharmaceuticals, Inc.; Sanofi