Effects on major adverse cardiovascular events (MACE) in persons treated with sotagliflozin: Prespecified pooled analyses of the Phase 3 type 2 diabetes program

Abstract

Background: In the SCORED trial that included 10,584 participants with type 2 diabetes (T2D) and chronic kidney disease (CKD), sotagliflozin significantly reduced the incidence of major adverse cardiovascular events (MACE). To further evaluate the cardiovascular effects of sotagliflozin, prespecified MACE-focused meta-analyses were performed using data from 9 additional Phase 3 trials conducted in persons with T2D.

Methods: This patient-level meta-analyses pooled data from 9 Phase 3 trials assessing glycemic control and other cardiometabolic parameters in a total of 5,100 participants. 2,904 participants were treated with sotagliflozin (pooling 200 and 400mg doses), while 2,196 were in an All-Comparators group (pooling placebo, empagliflozin, and glimepiride). Time to first event for 4-point MACE [CV death, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalization for unstable angina) was the prespecified primary analysis. Secondary outcomes included 3-point MACE (omitting unstable angina) and analyses of each MACE component outcome. Time-to-event analyses were conducted using Cox proportional hazards models for the first occurrence of any adjudication-confirmed event.

Results: There were 98 4-point MACE events and 96 3-point MACE events across the dataset. Event rate of 4-point MACE was 1.6 events per 100 patient-years (PY) in the sotagliflozin group compared with 2.2 events per 100 PY in the All-Comparators group. Sotagliflozin was associated with a 39% relative risk reduction in 4-point MACE (hazard ratio (HR) [95% CI]: 0.61 [0.41, 0.90]; p=0.013). All four component outcomes positively contributed to the overall treatment effect. For 3-point MACE, sotagliflozin demonstrated a 37% relative risk reduction compared with All-Comparators (HR [95% CI]: 0.63 {0.42, 0.94]).

Conclusion: Two independent data sources (9 cardiometabolic Phase 3 studies and the SCORED CV outcomes trial), including approximately 15,000 participants, support a reduction in MACE with sotagliflozin in a broad group of persons with T2D, and reinforce the role of sotagliflozin in reducing atherosclerotic cardiovascular risk.