Sotagliflozin: First SGLT inhibitor to show ischaemic benefit

The dual sodium–glucose co-transporter (SGLT) 1/2 inhibitor sotagliflozin appears to reduce the risk of major adverse cardiovascular events (MACE), especially myocardial infarction and stroke—a benefit that has not been previously observed with other drugs of the same class—in patients with type 2 diabetes, chronic kidney disease, and additional cardiovascular risk, according to the secondary analysis of the SCORED trial.

SCORED included 10,584 patients (median age 69 years, 44.9 percent female) who were randomly assigned to receive treatment with oral sotagliflozin (n=5,292) or placebo (n=5,292). Sotagliflozin was administered at a dose of 200 mg once a day, with the dose increased to 400 mg once a day within the first 6 months if tolerated. Matching placebo was given at the same frequency as sotagliflozin.

MACE, the prespecified secondary outcome, was defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, evaluated as first and subsequent events. Other outcomes were total myocardial infarction and total stroke (fatal and nonfatal events) as individual post hoc endpoints.

A total of 5,144 patients (48.6 percent) had a history of cardiovascular disease, including 2,108 (19.9 percent) with a history of myocardial infarction, 946 (8.9 percent) with a history of stroke, and 2,375 (22.4 percent) with a history of coronary revascularization.

Total MACE occurred with significantly less frequency with sotagliflozin than with placebo (4.8 vs 6.3 events per 100 person-years; hazard ratio [HR], 0.77, 95 percent confidence interval [CI], 0.65–0.91; p=0.0020). Interaction analyses indicated a consistent effect of sotagliflozin on total MACE across stratified subgroups without evidence of heterogeneity.

Of note, sotagliflozin exerted a significant effect on myocardial infarction (1.8 vs 2.7 events per 100 person-years; HR, 0.68, 0.52–0.89; p=0.0041) and stroke (1.2 vs 1.8 events per 100 person-years; HR, 0.66, 0.48–0.91; p=0.012) compared with placebo.

More studies are needed to examine combined SGLT1 and SGLT2 inhibition as a possible underlying mechanism.