Sotagliflozin: CV Benefit Seen in Patients with T2 Diabetes, Worsening Heart Failure

The sodium glucose contransporter-2 (SGLT-2) inhibitor sotagliflozin is associated with reduced cardiovascular (CV) mortality, hospitalizations, and urgent visits for care in patients with type 2 diabetes (T2D) and recent worsening heart failure, according to results of from the SOLOIST-WHF trial published online today in the New England Journal of Medicine.

SGLT2 inhibitors have proven effective in reducing the risk of hospitalization for heart failure (HFF) or death from CV causes among patients with stable heart failure. Lead study author Deepak Bhatt, MD, MPH, of Brigham and Women’s Hospital Heart and Vascular Center and colleagues evaluated the safety and efficacy of sotagliflozin when initiated soon after an episode of acute decompensated HF.

In the multicenter, double-blind randomized trial patients with T2D recently hospitalized for worsening heart failure were assigned 1:1 to receive sotagliflozin or placebo. The primary endpoint was total number of deaths from CV causes and hospitalizations and urgent visits for HF (first and subsequent events).

Eligibility criteria included hospital admission with decompensating HF, a prior diagnosis of T2D or diagnosis on admission. Patients with end-stage HF, or recent acute coronary syndrome, stroke, percutaneous coronary intervention or coronary-artery bypass surgery, or eGFR <30 ml/min/1.73 m2 were not eligible.

Of 1549 patients screened, 1222 were enrolled; average age was 69 years and 34% were women. 

After treatment randomization, there were 608 participants in the sotagliflozin group and 614 in the placebo group. Sotagliflozin was initiated at 200 mg daily and increased to a target dose of 400 mg daily unless side effects precluded titration. The drug was initiated either prior to hospital discharge (48.8%) or a median of 2 days post-discharge (51.2%).

Follow-up visits were scheduled at weeks 1, 2, and 4, at month 4, and then every 4 months. Patients were followed for a median of 9 months.

Results

• The primary end point was observed in 600 patients—245 in the sotagliflozin group and 355 in the placebo group.
• The rate of primary endpoint events—defined as the number of events per 100 patient-years—was lower in the sotagliflozin group than in the placebo group (51.0 vs. 76.3; hazard ratio [HR], 0.67; 95% CI, 0.52-0.85; P<.001).

Primary endpoint: total number of deaths from CV
causes and hospitalizations and urgent visits for HF.

• Rate of death from CV causes in the sotagliflozin arm was 10.6 vs 12.5 in the placebo cohort (HR, 0.84; 95% CI, 0.58-1.22).
• The rate of death from any cause was 13.5 for sotaglifozin and 16.3 for placebo (HR, 0.82; 95% CI, 0.59-1.14).

Diarrhea was more common in the sotagliflozin-treated group than the placebo group (6.1% vs 3.4%). The trend was similar for severe hypoglycemia (sotagliflozin, 1.5% vs placebo, 0.3%).

The proportion of patients with hypotension was similar in both groups (sotagliflozin, 6.0% vs placebo, 4.6%) as was the proportion with acute kidney injury (sotagliflozin, 4.1% and placebo, 4.4%).

Key limitation

Despite these encouraging findings, Bhatt and his team acknowledged the primary limitation which early termination of the trial related to loss of funding during the COVID-19 pandemic.

“Although the trial suggested that there was a beneficial effect with respect to the original primary end point of the first occurrence of either death from cardiovascular causes or hospitalization for heart failure, the earlier-than-planned closure of the trial limited the statistical power to assess the secondary end points, such as death from cardiovascular causes,” wrote Bhatt and colleagues.

The evidence that was accumulated during the study, they also said, suggests promise for initiation SGLT2 inhibitor therapy before or immediately following hospital discharge in patients with T2D and worsening heart failure.

“Early initiation of therapy represents an important opportunity to improve outcomes, as indicated by the high rate of primary end-point events at 90 days after randomization among the patients receiving placebo,” they wrote.