Dual SGLT1/2 Inhibitor Protects Against MI and Stroke

The dual sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor sotagliflozin reduced major adverse cardiovascular events, with significant reductions in the individual outcomes of myocardial infarction (MI) and stroke in patients with type 2 diabetes, chronic kidney disease, and other cardiovascular risk factors in a prespecified secondary analysis of the SCORED trial.

This ischemic benefit of sotagliflozin on both MI and stroke has not been observed in trials of selective SGLT2 inhibitors.

Sotagliflozin was approved in the United States in 2023 to reduce the risk for cardiovascular death, hospitalization for heart failure (HF) and urgent visits, and also for preventing these same events in patients with diabetes, kidney disease, and other cardiovascular risk factors.

The data from this prespecified analysis are “important” in demonstrating that the dual SGLT1/2 inhibitor also reduces the risk for MI and stroke, and “we could see more widespread use as a result,” SCORED Study Chair Deepak L. Bhatt, MD, MPH, director of Mount Sinai Fuster Heart Hospital in New York City, said in a news release.

“Few people had predicted the broad effects of the SGLT inhibitor class when initially developing a diabetes drug that increased glucose excretion in urine. Today, the well-known era of the SGLT inhibitor class, with extension of their diabetes indication to the prevention and treatment of heart failure and kidney disease even in patients without diabetes, is remarkable,” wrote the author of a comment published with the study online in The Lancet Diabetes & Endocrinology.

The SCORED Trial

In the SCORED trial, 10,584 patients with type 2 diabetes, chronic kidney disease, and risks for cardiovascular disease were randomly allocated to sotagliflozin or placebo and followed for a median of 16 months.

The primary result showed that sotagliflozin treatment cut the combined rate of deaths from cardiovascular causes, HF hospitalizations, and urgent visits by a significant 26% relative to placebo.

The prespecified analysis focusing on ischemic outcomes found that sotagliflozin led to a 23% reduction in adverse events — a composite of cardiovascular death, nonfatal MI, and nonfatal stroke — compared with placebo. The event rate per 100 person-years was 4.8 with sotagliflozin vs 6.3 with placebo (hazard ratio [HR], 0.77; P = .0020).

The dual SGLT1/2 inhibitor reduced the rate of MI by 32% (1.8 vs 2.7 events per 100 person-years; HR, 0.68; P = .0041) and stroke by 34% (1.2 vs 1.8 events per 100 person-years; HR, 0.66; P = 0.12).

The study team noted that biologic studies support SGLT1 inhibition as a potential mechanism for the ischemic benefit of sotagliflozin, although further investigation is needed to confirm this.

Comment authors Anna Norhammar, MD, PhD, and Viveca Ritsinger, MD, PhD, with Karolinska Institutet, Stockholm, Sweden, agreed that further study of the mechanisms behind the ischemic benefits seen is needed.

Norhammar and Ritsinger also noted that the SCORED trial included a high-risk population for MI with type 2 diabetes and chronic kidney disease, but only a fifth had HR-related criteria at baseline. “Therefore, these findings from the SCORED trial on the potential to prevent ischemic events are of importance for patients with type 2 diabetes,” they wrote.

“Apart from the findings on preventing ischemic events, this publication is a reminder that there can be valuable cooperation between academy and industry despite obstacles. There will be more to come in the field of cardiometabolic research; this we can predict,” they added.

The SCORED trial was funded by Lexicon Pharmaceuticals, which markets sotagliflozin under the trade name Inpefa. A complete list of disclosures for study and comment authors is available in the original article.