Diabetes drug shows CV benefit for patients with diabetes, HF

The sodium glucose cotransporter 1/2 inhibitor sotagliflozin reduced the primary composite endpoint of cardiovascular (CV) deaths, hospitalizations for heart failure (HF), and urgent visits for HF in patients with type 2 diabetes and HF, including those with HF with preserved ejection fraction (HFpEF; EF ≥50 percent), according to the pooled analysis of the SOLOIST* and SCORED** trials presented at ACC.21.

“Treatment with sotagliflozin robustly and significantly reduced CV adverse events across the full spectrum of patients with HF, including patients with HFpEF, for which no effective treatment is currently available,” said principal investigator Dr Deepak Bhatt from the Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts, US.

“The benefit for patients with HFpEF is striking – this is the first trial to find a significant benefit in this patient population,” Bhatt continued.

Bhatt and colleagues sought to determine if the benefits of sotagliflozin initially observed in both trials were consistent in those with HFpEF. Of the pooled SOLOIST and SCORED cohorts (n=11,784), 4,500 had a history of HF (HF subgroup). Both trials compared sotagliflozin 200 mg QD against placebo for a median follow-up duration of 9–16 months. [ACC.21, abstract 410-08]

In the pooled (intention-to-treat) analysis, there was a significant reduction in the primary composite endpoint among those treated with sotagliflozin compared with those receiving placebo (15.5 vs 21.1 events/100 patients; hazard ratio [HR], 0.72; p=0.000002). The findings were similar regardless of baseline EF (47.8 vs 60.4 events/100 patients; HR, 0.78; p=0.02 [HFrEF***], 45.2 vs 71.3 events/100 patients; HR, 0.61; p=0.003 [HFmrEF^#], and 37.5 vs 59.0 events/100 patients; HR, 0.70; p=0.0008 [HFpEF]).

The findings were similar in the HF subgroup, be it among individuals who had HFrEF (HR, 0.78; p=0.02), HFmrEF (HR, 0.57; p=0.002), or HFpEF (HR, 0.67; p=0.006).

HFpEF is particularly common in older women, noted Bhatt. When they stratified their findings by sex, they found a similar reduction in the primary composite endpoint with sotagliflozin vs placebo among women with HFpEF, both in the overall cohort (HR, 0.71) and in the HF subgroup (HR, 0.65).

However, the findings only apply to individuals who both have HF and diabetes, and may therefore not be generalizable to all patient populations, Bhatt noted. Early termination also cut the duration of the trials, thus limiting the statistical power to observe reductions in some endpoints.

Nonetheless, the reduction in the primary endpoint was robust, with a significant reduction in CV death on on-treatment analyses and a consistent benefit among women, Bhatt pointed out.

“The magnitude of the benefit in patients with HFpEF was surprising … We believe these results merit a recommendation that patients who have both diabetes and HFpEF should be treated with sotagliflozin or another medication in its class,” said Bhatt. “Sotagliflozin offers a meaningful, incremental advance in improving outcomes for this challenging group of patients.”