Sotagliflozin Cuts MACE Risk By 23% in Patients with Type 2 Diabetes, CKD

Deepak L. Bhatt, MD, MPH, MBA

Credit: Mount Sinai

Sotagliflozin, a dual sodium-glucose cotransporter (SGLT) 1/2 inhibitor, lowered the risk of major adverse cardiovascular events (MACE), including myocardial infarction and stroke, in a recent analysis of patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).¹

This prespecified analysis of the SCORED randomized trial, enrolling nearly 11,000 patients with additional cardiovascular risk, reported an approximate 23% reduction in the rate of myocardial infarction, stroke, and cardiovascular death, compared with the placebo group.²

“These results demonstrate a new mechanism of action—combined blockage with sotagliflozin of the SGLT1 receptors (found in the kidney, gut, heart, and brain) and SGLT2 receptors (found in the kidney) to reduce heart attack and stroke risk,” said Deepak L. Bhatt, MD, MPH, MBA, director of Mount Sinai Fuster Heart Hospital, in a statement.² “The benefits seen here are distinct from those seen with the other very population SGLT2 inhibitors in widespread clinical use for diabetes, heart failure (HF), and kidney disease.”

Sotagliflozin has been studied across multiple patient populations encompassing HF, T2D, and CKD, representing nearly 20,000 patients. The drug was approved by the US Food and Drug Administration (FDA) in May 2023 to lower the risk of cardiovascular death, hospitalization for HF, and urgent HF visits in these patient populations.³

The SCORED trial was a double-blind, placebo-controlled, randomized clinical trial that enrolled adults with T2D, CKD, and cardiovascular risk factors from 750 sites in 44 countries. Patients were randomly assigned to oral sotagliflozin 200 mg, with the dose increased to 400 mg within the first 6 months if tolerable, or placebo. A matching placebo was prescribed at the same treatment frequency as the intervention regimen.⁴

A prespecified secondary outcome of MACE was assessed as first and subsequent events, with total myocardial infarction and total stroke serving as individual post-hoc endpoints. For the analysis, outcomes were evaluated by intention-to-treat with competing-risk proportional hazards models for the overall population, and by total MACE, in prespecified subgroups by demographic and clinical features.¹

Enrolling 10,584 patients, the SCORED trial randomly assigned 5292 (50%) to sotagliflozin and 5292 (50%) to placebo between December 2017 and Jan 2020, with an average follow-up of 16 months. The population had a median age of 69 years and 4754 (44.9%) were female. A history of cardiovascular disease was present in nearly half (48.6%) of patients, of whom 19.9% had a history of myocardial infarction, 8.9% had a history of stroke, and 22.4% had a history of coronary revascularization.

Upon analysis, individuals receiving sotagliflozin experienced a significantly lower rate of total MACE than the placebo cohort (4.8 events vs. 6.3 events per 100 person-years; hazard ratio [HR], 0.77 [95% CI, 0.65–0.91]; P =.0020). These effects on total MACE were consistent among stratified subgroups, with no evidence of heterogeneity.

Treatment with sotagliflozin also significantly lowered the rate of myocardial infarction (1.8 events vs. 2.7 events per 100 person-years; HR, 0.68 [95% CI, 0.52–0.89]; P =.0041) and stroke (1.2 events vs. 1.8 events per 100 person-years; HR, 0.66 [95% CI, 0.48–0.91]; P =.012), compared with placebo.

With these data, Bhatt and colleagues pronounced sotagliflozin the first SGLT inhibitor to demonstrate ischemic benefit on both myocardial infarction and stroke risk. As a result, the team called for further investigation of combined SGLT1 and SGLT2 inhibition as a possible underlying mechanism of this risk reduction.²

“This drug was approved to reduce the risk of deaths from cardiovascular causes, hospitalizations for HF, and urgent HF visits for patients with either HF or T2D,” Bhatt added.² “These important, new data show that it additionally reduces the risk of heart attacks and strokes, and we could see more widespread use as a result.”

References

1. Aggarwal R, Bhatt DL, Szarek M, et al. Effect of sotagliflozin on major adverse cardiovascular events: a prespecified secondary analysis of the SCORED randomised trial. Lancet Diabetes Endocrinol. Published online February 13, 2025. doi:10.1016/S2213-8587(24)00362-0

2. IcahnMountSinai. A diabetes, heart failure, and kidney disease medication is the first of its kind to significantly reduce both heart attacks and strokes. EurekAlert! February 14, 2025. Accessed February 18, 2025. https://www.eurekalert.org/news-releases/1073500.

3. Campbell P. FDA approves Sotagliflozin for treatment of heart failure. HCP Live. May 26, 2023. Accessed February 18, 2025. https://www.hcplive.com/view/fda-approves-sotagliflozin-for-treatment-of-heart-failure.

4. Lexicon Pharmaceuticals, Inc. Published data in the lancet diabetes & endocrinology highlights unique efficacy benefits of Sotagliflozin to reduce major adverse cardiovascular events (MACE). GlobeNewswire News Room. February 18, 2025. Accessed February 18, 2025. https://www.globenewswire.com/news-release/2025/02/18/3027794/0/en/Published-Data-in-The-Lancet-Diabetes-Endocrinology-Highlights-Unique-Efficacy-Benefits-of-Sotagliflozin-to-Reduce-Major-Adverse-Cardiovascular-Events-MACE.html.