Semaglutide Found Effective for Weight Loss in Patients With Heart Failure, Obesity

Semaglutide is a pharmacologic treatment that could be effective for weight loss for patients who have heart failure (HF) with preserved ejection fraction and obesity, according to the results of a randomized, placebo-controlled study published in the New England Journal of Medicine.

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Patients on semaglutide lost more than 5-times the percentage of weight that was lost by participants in the placebo arm, and the pharmacologic agent significantly improved physical limitations and exercise function, the authors observed.

“Our findings of substantial reductions in symptoms and physical limitations and improvements in exercise function that parallel a greater degree of weight loss with semaglutide than with placebo may offer insights into the long-standing controversy surrounding weight (and weight loss) in persons with HF,” the study authors wrote in the article.

They added that most patients who are experiencing HF with preserved ejection have obesity, and new evidence considers obesity to be a contributing factor to HF with preserved ejection fraction. Having obesity and HF with preserved ejection fraction is also linked to worse functional capacity and quality of life. Worse physical function is independently linked to hospitalization, poor quality of life, and even death, the investigators noted.

“Reductions in symptoms and improvements in physical function are therefore…as important as avoidance of death and hospitalizations,” the authors wrote.

The Effect of Semaglutide 2.4 mg Once Weekly on Function and Symptoms in Subjects with Obesity-related Heart Failure with Preserved Ejection Fraction (STEP-HFpEF) trial evaluated semaglutide for HF-related symptoms and physical limitations and percentage of weight loss in this patient population.

For 52 weeks, investigators randomized 529 patients who have HF with preserved ejection fraction and a body mass index (BMI) of 30 or more to receive once-weekly semaglutide (2.4 mg) or placebo. Investigators selected primary endpoints of 1) a change from base­line in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and 2) a change in body weight.

After 1 year, the mean KCCQ-CSS score—which measures physical limitations on a scale of 0 to 100 (most to least symptoms)—was 16.6 points with semaglutide and 8.7 with placebo. Patients on semaglutide lost a statistically significant 13.3% of body weight, whereas the placebo arm lost an average of 2.6% body weight (estimated difference, −10.7 percentage points; 95% CI, −11.9 to −9.4; P<0.001).

STEP-HFpEF defined key secondary endpoints as 1) a change in 6-minute walk distance, 2) a hierarchical composite of death, HF events, and differences in the change in the KCCQ-CSS and 6-minute walk distance, and 3) the change in the C-reactive protein (CRP) level.

The mean change in 6-minute walk distance was 21.5 m and 1.2 m in the semaglutide and placebo groups, respectively. Further, semaglutide was more favorable for all components of the composite endpoint, including death and HF events.

In addition, more than double the percentage of patients in the placebo cohort had serious adverse events compared to patients in semaglutide cohort (26.7% and 13.3%; P<0.001). The results ultimately suggest that semaglutide improved both weight loss and pathophysiological processes underlying HF, according to the study.

“Whether this is also the case with other types of weight loss interventions or in other populations will be useful to evaluate in future trials,” the study authors concluded.

Reference

Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med;2023; DOI: 10.1056/NEJMoa2306963.