Major Adverse Cardiovascular Events Across the Sotagliflozin Clinical Development Program

Abstract

SGLT inhibitors, including sotagliflozin, have been shown to consistently reduce the risk of heart failure (HF) and renal-related events. Their effects on major adverse cardiovascular events (MACE: myocardial infarction [MI] and stroke) have been variable. Sotagliflozin was the first SGLT inhibitor to demonstrate a significant reduction in both MI and stroke in adults with type 2 diabetes (T2D) and chronic kidney disease. The objective of this analysis was to evaluate the effect of sotagliflozin on MACE across sotagliflozin clinical program, which included Phase 2 and Phase 3 clinical trials with 20,292 patients with T2D or type 1 diabetes (T1D). SCORED and SOLOIST were Phase 3, randomized, double-blind, studies evaluating sotagliflozin and placebo in 10,584 patients with T2D, chronic kidney disease, and other CV risk factors and 1,222 patients with T2D admitted for a worsening heart failure event, respectively. In addition, three Phase 3 placebo-controlled trials were conducted in 3,000 patients with T1D. Nine Phase 3 placebo- and active controlled studies evaluated sotagliflozin in 5,100 patients with T2D. The present analysis focuses on 3-point MACE (CV death, non-fatal MI, and non-fatal stroke). Meta-analysis was performed using a fixed effects model. SCORED contributed the most events to the analysis. MACE results for each dataset significantly or numerically favored sotagliflozin. Overall, the composite of 3-point MACE was lower with sotagliflozin compared with comparator (HR [95% CI] = 0.79 [0.68, 0.90]) (Table). In summary, treatment with sotagliflozin was associated with a significant reduction in MACE in patients with T1D and T2D.