Semaglutide 2.4 mg Improves Functional Status, Body Weight in Adults with HFpEF, Obesity, T2D

Among adults with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes, semaglutide 2.4 mg (Wegovy; Novo Nordisk) led to greater reductions in heart failure–related symptoms and physical limitations and greater weight loss compared to placebo at 1 year, according to findings of the STEP HFpEF DM trial¹ presented at the American College of Cardiology Annual Scientific Sessions, April 6-8, 2024, in Atlanta, GA.

“Obesity forms a ‘common soil’ that can lead to the development of heart failure with preserved ejection fraction and type 2 diabetes, and patients living with both conditions suffer from an especially high symptom burden but have few available treatment options,” Mikhail Kosiborod, MD, lead study investigator and cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, MO, said in a statement.²

The study follows the original STEP HFpEF, study published in 2023, that compared effects of semaglutide 2.4 mg vs placebo on symptoms and functional status in adults with obesity and HFpEF, regardless of diabetes status, with results favoring semaglutide on primary and secondary outcomes.2 Sematglutide-treated participants reached a 16.6-point increase on the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 52 weeks vs an 8.7-point increase for those treated with placebo (P <.001). The semaglutide group also had a mean 13.3% reduction in body weight compared to 2.6% for those in the placebo group.²

For the current study, published simultaneously in the New England Journal of Medicine,¹ Kosiborod and colleagues randomly assigned 616 adults with HFpEF, body mass index (BMI) of 30 kg/m² or greater, and T2D in a 1:1 ratio to receive once-weekly subcutaneous semaglutide 2.4 mg or placebo for 52 weeks.

Like STEP HFpEF, STEP HFpEF DM defined coprimary endpoints: change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and change in body weight. The researchers also defined the same multiple confirmatory secondary end points, including change in 6-minute walk distance (6MWD); a hierarchical composite end point that included death, HF events, and differences in the change in the KCCQ-CSS and 6MWD; and the change in level of C-reactive protein (CRP).¹

FINDINGS

Kosiborod et al reported a mean change from baseline KCCQ-CSS of 13.7 points with semaglutide 2.4 mg and 6.4 points with placebo (estimated treatment difference [ETD], 7.3 points; 95% CI, 4.1 to 10.4; P < .001).¹ Changes in body weight from baseline also favored the study drug at −9.8% with semaglutide and −3.4% with placebo therapy (ETD, −6.4 percentage points; 95% CI, −7.6 to −5.2; P < .001).¹ Results for the secondary confirmatory endpoints also showed superiority over placebo for semaglutide 2.4 mg¹:

• change in 6MWD: estimated between-group difference, 14.3 meters; 95% CI, 3.7 to 24.9; P =.008
• hierarchical composite endpoint: win ratio, 1.58; 95% CI, 1.29 to 1.94; P < .001
• change in CRP level: estimated treatment ratio, 0.67; 95% CI, 0.55 to 0.80; P < .001

According to the study results, the safety profile of semaglutide 2.4 mg was consistent with findings of previous studies; there were fewer serious adverse events in the semaglutide-treated group than in the placebo group, according to the statement.²

“Today’s results, especially when combined with those from the STEP-HFpEF trial, open a new chapter of targeting obesity as a new and effective treatment strategy in patients with obesity-related HFpEF, both with and without diabetes.”²

References

1. Semaglutide in patients with obesity-related heart failure and type 2 diabetes. N Engl J Med. Published online April 6, 2024. doi: 10.1056/NEJMoa2313917
2. Semaglutide 2.4 mg demonstrates large reductions in heart failure related symptoms and physical limitations in people with obesity-related heart failure with preserved ejection fraction and type 2 diabetes. News release. St Luke's Mid America Heart Institute. April 6, 2024. Accessed April 8, 2024. https://www.saintlukeskc.org/about/news/semaglutide-24-mg-demonstrates-large-reductions-heart-failure-related-symptoms-and