Abstract 13696: Sotagliflozin is Associated With Early Clinical Benefit for Heart Failure and Atherosclerotic Events

Abstract

Background: SGLT inhibitors reduce cardiovascular (CV) death and heart failure (HF)-related outcomes in HF patients, with benefits observed within 1 month. Less data exist for the time to clinical benefit for reducing HF or major cardiovascular events (MACE; CV death, myocardial infarction, and stroke) with SGLT inhibitors in patients with chronic kidney disease at high CV risk. Objective: This analysis evaluates the time to clinical benefit for HF-related events and MACE with sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, in SCORED. Methods: SCORED was a randomized, double-blind study of 10,584 patients with type 2 diabetes, chronic kidney disease, and other CV risk factors, where patients were randomized 1:1 to sotagliflozin or placebo. The primary endpoint was total CV death, hospitalization for HF, or urgent visit for HF. A prespecified secondary endpoint was total MACE. The present post hoc analysis calculated the sotagliflozin:placebo hazard ratios (HR) and 95% confidence intervals (CI) for each of these outcomes and determined the day after randomization where the treatment effect reached statistical significance (p<0.05) and remained statistically significant for the duration of follow-up. Results: The overall risk of the primary endpoint was reduced by 26% (HR (95% CI) = 0.74 (0.63, 0.88); p<0.001) with sotagliflozin, with a sustained significant reduction 95 days after randomization (HR (95% CI) = 0.70 (0.50, 0.98) at 95 days; Figure A). For MACE, the overall risk reduction with sotagliflozin was 23% (HR (95% CI) = 0.77 (0.65, 0.91); p<0.001), with a sustained significant reduction 94 days after randomization (HR (95% CI) = 0.69 (0.47, 0.99) at 94 days; Figure B). Conclusion: In this stable, outpatient population at high risk for CV events, the time to clinical benefit with sotagliflozin was very early at approximately three months for both HF- and MACE-related outcomes.