Kansas City, MO—Treatment with the diabetes drug semaglutide shows promise for improving care for obese patients with HFpEF.

A new study in the New England Journal of Medicine reports that doses of semaglutide (2.4 mg) result in significant reductions in symptoms and physical limitations, greater improvements in exercise function, and greater weight loss compared with placebo.

That is especially important, according to the University of Missouri-Kansas City School of Medicine–led research, because HFpEF is increasing in prevalence and is associated with a high symptom burden and functional impairment, especially in the obese. Up to this point, no specific therapies have been approved to target obesity-related HFpEF, according to the industry-funded trial.

For the study, researchers randomly assigned 529 patients who had HFpEF and a BMI of 30 or higher to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. Their focus was on the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight.

As confirmation of effectiveness, the study team also designated secondary endpoints, including the change in the 6-minute walk distance; a hierarchical composite endpoint that included death, HF events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level.

The results indicated that the mean change in the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points; 95% CI, 4.8-10.9; P <.001), and the mean percentage change in body weight was –13.3% with semaglutide and –2.6% with placebo (estimated difference, –10.7 percentage points; 95% CI, –11.9 to –9.4; P <.001).

In terms of other endpoints, the mean change in the 6-minute walk distance was 21.5 m with semaglutide and 1.2 m with placebo (estimated difference, 20.3 m; 95% CI, 8.6-32.1; P <.001). “In the analysis of the hierarchical composite endpoint, semaglutide produced more wins than placebo (win ratio, 1.72; 95% CI, 1.37-2.15; P <.001),” the authors wrote. “The mean percentage change in the CRP level was –43.5% with semaglutide and –7.3% with placebo (estimated treatment ratio, 0.61; 95% CI, 0.51-0.72; P <.001). Serious adverse events were reported in 35 participants (13.3%) in the semaglutide group and 71 (26.7%) in the placebo group.”

Background information in the article pointed out that HFpEF makes up more than one-half of all cases of HF in the U.S. “The majority of persons with the condition have overweight or obesity, and growing evidence suggests that obesity and excess adiposity are not simply coexisting conditions but may play a role in the development and progression of heart failure with preserved ejection fraction,” the researchers explained. “Patients with this condition and obesity have more adverse hemodynamic and clinical features and a greater symptom burden, worse functional capacity, and more severely impaired quality of life than those with heart failure with preserved ejection fraction but no obesity.”

The study team explored the question of whether the use of pharmacotherapies that specifically target obesity can reduce symptoms and physical limitations and improve exercise function in those patients. The team noted that “once-weekly semaglutide at a dose of 2.4 mg administered subcutaneously is a potent glucagon-like peptide 1 receptor agonist that is approved for long-term weight management and has previously been shown to produce major weight loss in persons with overweight or obesity and to have favorable effects on cardiometabolic risk factors.”

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

« Click here to return to Weekly News.