Sotagliflozin Reduced MACE Risk in Patients With and Without Prior CVD, in New Analysis of SCORED Clinical Trial

Updated findings from the SCORED phase III clinical trial presented at the American College of Cardiology’s (ACC) 71st Annual Scientific Session offered new insights on the benefits of sotagliflozin (Zynquista®, Lexicon Pharmaceuticals) in patients with type 2 diabetes mellitus (T2D) and chronic kidney disease (CKD).

In the SCORED clinical trial, 10 584 (mean age, 69 years; 45% women) patients with T2D and CKD were randomized to either sotagliflozin 400 mg daily or placebo for a median of 16 months. Treatment with sotagliflozin, an investigational dual sodium glucose cotransporter (SGLT)-1 and SGLT-2 inhibitor, resulted in a significant reduction in major adverse cardiovascular events (MACE) of cardiovascular (CV) death, myocardial infarction (MI), and stroke.

The current analysis examined the effect of sotagliflozin on MACE in prespecified subgroups of patients with cardiovascular disease (CVD; n=5144) and without CVD (n=5440) at baseline.

“This analysis demonstrated that in addition to reducing heart failure events, sotagliflozin reduced MACE events,” said study chair Deepak L. Bhatt, MD, MPH, executive director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital, in a Lexicon press release. “The lower rates of MACE, notably including reductions in both heart attack and stroke, were consistent in patients with and without cardiovascular disease at baseline.”

Bhatt presented the new findings at ACC.22 which followed his team’s assessment of the risk of total MACE, total MI, and total stroke from SCORED in groups they stratified based on CVD history.

Bhatt reported that sotagliflozin was associated with a 21% relative risk reduction in total MACE, total MI, and total stroke among patients with a history of CVD (HR, 0.79 [95% CI, 0.64-0.96]; P=.02) and a 26% relative risk reduction among those without CVD (HR, 0.74 [95% CI, 0.56-0.99]; P=.046).

The analysis of data for total MI found a reduced risk of 31% among participants taking sotagliflozin who had CVD (HR, 0.69 [95% CI, 0.51-0.95]; P=.023) and of 34% among those without CVD (HR, 0.66 [95% CI, 0.41-1.06]; P=.088). When they evaluated total stroke, Bhatt and colleagues found risk was reduced by 31% in those with CVD (HR, 0.69 [95% CI, 0.46-1.02]; P=.063) and by 38% in those without CVD (HR, 0.62 [95% CI, 0.36-1.06]; P=.08).

Adverse events included urinary tract infections, diarrhea, volume depletion, and bone fractures. Of note, researchers reported a significant increase in diarrhea among those taking sotagliflozin (8.5%) compared to placebo (6%).

Sotagliflozin is not yet approved by the US Food and Drug Administration (FDA), although it has been authorized for type 1 diabetes by the European Medical Agency. Lexicon Pharmaceuticals has filed for FDA approval in the US.

Bhatt presented the study, “Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk – SCORED” on April 2, 2022, as part of the Featured Clinical Research I session.