Composite risk for hospitalization or an urgent visit due to heart failure (HF) and cardiovascular-related mortality decreased with sotagliflozin therapy among patients with diabetes and chronic kidney disease comorbidities. These findings, from a multicenter, phase 3, double-blind trial, were published in The New England Journal of Medicine.
Patients (N=10,584) with type 2 diabetes mellitus, chronic kidney disease, and cardiovascular disease risk factors were recruited at 750 centers in 44 countries between late 2017 and early 2020. Patients were randomized to receive 200 mg daily sotagliflozin (n=5292) or placebo (n=5292). The daily dose of sotagliflozin was increased to 400 mg if no adverse effects were reported. Patients received a median of 14.2 (interquartile range [IQR], 10.3-18.9) and 14.3 (IQR, 10.3-18.9) months of sotagliflozin or placebo, respectively. Patients were assessed for clinical characteristics and cardiovascular events.
Patients had a median age of 69 years; 44.9% were women, and 82.7% were White. Most patients assigned to the treatment group (74.5%) increased their dose from 200 mg to 400 mg. Early termination from the study occurred among 10.9% of the treatment and 11.3% of the placebo cohorts.
At baseline, patients’ median glycated hemoglobin was 8.3%, body mass index was 31.8 kg/m2, estimated glomerular filtration rate was 44.5 (IQR, 37.0-51.4) ml/min/1.73 m2, urinary albumin-to-creatinine ratio was 74 (IQR, 17-481), and left ventricular ejection fraction was 60% (IQR, 51%-65%); 19.9% of patients had an ejection fraction of 40% or less or had been hospitalized for HF during the previous 2 years.
The incidence of cardiovascular-related deaths, and hospitalizations and urgent visits for HF, was 5.6 and 7.5 per 100 person-years in the treatment and placebo groups, respectively. This indicates that sotagliflozin decreased the primary end-point risk (hazard ratio [HR], 0.74; 95% CI, 0.63-0.88; P <.001).
The incidence of hospitalizations and urgent visits due to HF was lower among the treatment recipients (3.5 events per 100 person-years) than placebo recipients (5.1 events per 100 person-years), with a HR of 0.67 (95% CI, 0.55-0.82; P <.001). Cardiovascular-related mortality alone was not significantly lower among sotagliflozin recipients (HR, 0.90; 95% CI, 0.73-1.12).
Although rates of serious adverse events (23.4% vs 25.2%) were similar between groups, patients receiving sotagliflozin reported more diarrhea (8.5% vs 6.0%; P <.001), genital mycotic infections (2.4% vs 0.9%; P <.001), volume depletion (5.3% vs 4.0%; P =.003), hypotension (2.6% vs 1.9%; P =.009), and diabetic ketoacidosis (0.6% vs 0.3%; P =.02).
This study was limited by funding difficulties that caused the investigators to prematurely end the trial and redefine the study end points due to lack of power.
These data indicated sotagliflozin lowered the composite risk for hospitalization or urgent visits for HF and cardiovascular-related mortality among patients with type 2 diabetes with chronic kidney disease and cardiovascular risk factors.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Bhatt DL, Szarek M, Pitt B, et al; SCORED Investigators. Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med. 2021;384:129-139. doi:10.1056/NEJMoa2030186