Sotagliflozin Reduces MACE in T2DM, CKD, CVD Risk Patients

On March 3, 2025, a noteworthy study revealed promising outcomes for patients with type 2 diabetes, chronic kidney disease, and additional cardiovascular risk factors. The research focused on sotagliflozin, a dual sodium-glucose co-transporter (SGLT)-1/2 inhibitor, which demonstrated a significant reduction in major adverse cardiovascular events (MACE). These findings were published online on February 14 in The Lancet Diabetes & Endocrinology.

The study was spearheaded by Rahul Aggarwal, M.D., from Harvard Medical School, along with his research team. They performed a preplanned secondary analysis of the SCORED trial, a methodically structured double-blind and randomized investigation. This trial involved adult participants diagnosed with type 2 diabetes, chronic kidney disease, and additional cardiovascular risk factors. Between December 8, 2017, and January 20, 2020, 10,584 patients across 750 locations in 44 countries were randomly assigned to receive either sotagliflozin or a placebo, with 5,292 participants in each group.

The analysis revealed that those treated with sotagliflozin experienced a noteworthy reduction in the incidence of total MACE compared to the placebo group. Specifically, the sotagliflozin group had an incidence rate of 4.8 events per 100 person-years, compared to 6.3 events in the placebo group. This translated to a hazard ratio of 0.77, indicating a significant protective effect of sotagliflozin. Importantly, the beneficial effects of sotagliflozin on total MACE were consistent across various subgroups, without any signs of variability.

Moreover, sotagliflozin significantly lowered the risk of myocardial infarction and stroke. The incidence of myocardial infarction among sotagliflozin users was 1.8 events per 100 person-years, as opposed to 2.7 events in the placebo group, corresponding to a hazard ratio of 0.68. Similarly, the occurrence of strokes was reduced to 1.2 events per 100 person-years in the sotagliflozin group, compared to 1.8 events in the placebo group, with a hazard ratio of 0.66.

The study's authors highlighted that the ischemic benefits observed with sotagliflozin, particularly in reducing strokes and myocardial infarctions, had not been previously documented in trials involving selective SGLT-2 inhibitors. This suggests the potential of SGLT-1 inhibition as a contributing mechanism, warranting further exploration.

It is noteworthy that some authors of the study disclosed connections with pharmaceutical companies, including Lexicon Pharmaceuticals, the manufacturer of sotagliflozin, which also provided funding for the research. The findings of this study offer promising insights into the benefits of sotagliflozin for patients with complex medical conditions, highlighting its potential role in mitigating cardiovascular risks. Further research could deepen our understanding of the mechanisms behind these beneficial effects and expand therapeutic options for affected patients.