Semaglutide effective treatment for HFpEF in people with type 2 diabetes

Results from the STEP-HFpEF-DM trial presented at the ADA 84^th Scientific Sessions suggest that the GLP-1 receptor agonist semaglutide is effective for treatment of obesity-related heart failure with preserved ejection fraction (HFpEF) in people with type 2 diabetes.

Previous research had suggested semaglutide was effective in people without diabetes who had obesity and HFpEF (Kosiborod et al, 2023); however, there had been concerns that efficacy might be lower in people with type 2 diabetes, given that the weight-lowering effects of semaglutide are reduced in people with diabetes versus those without the condition.

A total of 616 adults with type 2 diabetes, obesity and HFpEF (left ventricular ejection fraction of at least 45%) were randomised to semaglutide 2.4 mg or placebo for 52 weeks. Median age was 69 years, BMI 36.9 kg/m² and HbA_1c 51 mmol/mol (6.8%). Most participants were receiving diuretics, RAAS blockers and beta-blockers, and around a third were receiving an MRA and/or an SGLT2 inhibitor.

The dual primary endpoints were the percentage change in body weight and the change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) – an indicator of HF symptoms, physical function, social function and quality of life, with scores ranging from 0 (worst) to 100 (best).

At 52 weeks, for the treatment policy estimand (similar to an intention-to-treat analysis), KCCQ-CSS improved, from a baseline of around 60 points, by 13.7 points and 6.4 points in the semaglutide and placebo groups, respectively (estimated difference 7.3 points; P<0.001). Notably, the treatment difference was 8.3 points in people not taking SGLT2 inhibitors at baseline and 5.3 points in those who were, suggesting some benefit of combining the two drug classes in this patient group.

Mean weight loss at 52 weeks was 9.8% in the semaglutide group versus 3.4% in the placebo group (estimated treatment difference 6.4%), which was about 40% less than in the STEP-HFpEF trial conducted in people without type 2 diabetes (Kosiborod et al, 2023).

Among the prespecified secondary endpoints, 6-minute walk distance improved in the semaglutide group compared with placebo, as did C-reactive protein levels. Serious adverse event rates were significantly lower in the semaglutide group (17.7% vs 28.8%). One limitation of the study was that it was not powered to assess clinical outcomes (e.g. hospitalisation for heart failure); however, these favoured semaglutide.

The authors concluded that the previously demonstrated benefits of semaglutide for HFpEF extend to people with type 2 diabetes, resulting in significant reductions in HF-related symptoms and physical limitations, weight loss, and improvements in exercise function.

The findings were published in the New England Journal of Medicine.