Dual SGLT1/2 Inhibitor Sotagliflozin Lowers Risk of Myocardial Infarction and Stroke

A recent secondary analysis of the SCORED trial evaluated whether sotagliflozin, a dual sodium–glucose co-transporter (SGLT) 1/2 inhibitor, improves ischemic cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease.

SGLT2 inhibitors have consistently demonstrated benefits in heart failure-related outcomes but have not shown significant reductions in ischemic cardiovascular events such as myocardial infarction and stroke. Given this gap, researchers assessed whether sotagliflozin, which also inhibits SGLT1, could provide additional cardiovascular protection beyond traditional SGLT2 inhibitors.

This prespecified secondary analysis of the double-blind, placebo-controlled, randomized SCORED trial included 10,584 adults with type 2 diabetes, chronic kidney disease (estimated glomerular filtration rate [eGFR] 25–60 mL/min per 1.73 m²), and additional cardiovascular risk factors. Participants were randomly assigned to receive sotagliflozin (200 mg once daily, increased to 400 mg if tolerated) or a placebo. The primary outcome for this analysis was total major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Additional outcomes included total myocardial infarction and stroke, analyzed individually.

Patients in the sotagliflozin group had a significantly lower rate of total MACE compared with those receiving placebo (4.8 vs 6.3 events per 100 person-years; HR, 0.77 [95% CI, 0.65–0.91]; P = .0020). The risk of myocardial infarction was reduced by 32% (HR, 0.68 [0.52–0.89]; P = .0041), while the risk of stroke decreased by 34% (HR, 0.66 [0.48–0.91]; P = .012). These effects remained consistent across patient subgroups stratified by demographic and clinical characteristics.

The study's limitations include its secondary analysis design, which may not establish causality, and the early termination of the trial due to funding constraints, potentially limiting long-term outcome assessment.

“Sotagliflozin reduced MACE, with independent reductions in myocardial infarction and stroke, among patients with type 2 diabetes, chronic kidney disease, and additional cardiovascular risk,” the authors concluded. “The ischemic benefit on both myocardial infarction and stroke has not been previously observed with other SGLT inhibitors and warrants investigation of combined SGLT1 and SGLT2 inhibition as a possible underlying mechanism.”

Reference

Aggarwal R, Bhatt DL, Szarek M, eta l. Effect of sotagliflozin on major adverse cardiovascular events: a prespecified secondary analysis of the SCORED randomised trial. Lancet Diabetes Endocrinol. 2025:S2213-8587(24)00362-0. doi:10.1016/S2213-8587(24)00362-0