Ischemic Cardiovascular Outcomes Improved With Dual SGLT Inhibitor

The benefit in improving heart failure-related outcomes with sodium-glucose cotransporter (SGLT)-2 inhibitors is well established. However, there are few data available on the benefit of those agents in ischemic cardiovascular events such as myocardial infarction or stroke. Rahul Aggarwal, MD, and colleagues performed a prespecified secondary analysis of the SCORED trial to assess whether sotagliflozin, a dual SGLT-1/2 inhibitor, improves outcomes for patients experiencing ischemic cardiovascular events.

The trial cohort included adult patients with type 2 diabetes, chronic kidney disease (estimated glomerular filtration rate [eGFR] 25-60 mL/min/1.73 m²), and additional cardiovascular risk factors at 750 sites in 44 countries. Participants were randomly assigned 1:1 to oral sotagliflozin 200 mg once a day, increased to 400 mg once a day within 6 months if tolerated, or placebo. A prespecified secondary outcome was total major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke.

A total of 10,584 patients were enrolled (sotagliflozin: n=5,292; placebo: n=5,292). Median age of the overall cohort was 69 years, 44.9% were female, 48.6% had a history of myocardial infarction, 8.9% had a history of stroke, and 22.4% had a history of coronary revascularization. The rate of total MACE was significantly lower among patients in the sotagliflozin group than in the placebo group (4.8 events per 100 person-years vs 6.3 events per 100 person-years; HR, 0.77; 95% CI, 0.65-0.91; P=0.002).

Results of interaction analyses among groups stratified by baseline demographic and clinical features, heart-related criteria, eGFR, urine albumin-creatinine ratio, and history of cardiovascular disease suggested a consistent effect of sotagliflozin in total MACE without evidence of heterogeneity. The rates of myocardial infarction and stroke were reduced compared with placebo.

“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 ischemic benefit on myocardial infarction and stroke has not been previously observed with other SGLT inhibitors and warrants investigation of combined SGLT1 and SGLT2 inhibitors as a possible underlying mechanism,” the authors said.

Source: Aggarwal H, et al. Lancet Diabetes Endocrinol. 2025 Apr;13(4):321-332. doi:10.1016/S2213-8587(24)00362-0