Sex differences in weight loss, not health with semaglutide in heart failure with obesity
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Key takeaways:
- Women with obesity and HF lost 9.6% of body weight with semaglutide vs. 7.2% for men.
- Men and women had similarly improved HF symptoms.
ORLANDO — Among adults with obesity-related heart failure with preserved ejection fraction, women taking semaglutide lost significantly more weight than men, but greater weight loss did not result in extra health benefits for women vs. men.
In the STEP-HFpEF trials, women had worse baseline health status and exercise capacity than men but lost more weight with semaglutide 2.4 mg (Wegovy, Novo Nordisk) than men did, according to Subodh Verma, MD, PhD, FRCSC, professor and the Canada Research Chair in Cardiovascular Surgery at the University of Toronto.
Verma presented the new data at the American Diabetes Association Scientific Sessions during a symposium exploring the implications of findings from the STEP-HFpEF trials for targeting obesity to treat heart failure.
In the new study, simultaneously published in the Journal of the American College of Cardiology, semaglutide was associated with similarly improved HF-related symptoms, BMI and physical limitations vs. placebo for both sexes without regard to the magnitude of weight loss.
As Healio previously reported, in the STEP-HFpEF trial of adults with obesity-related heart failure with preserved ejection fraction (HFpEF; defined as BMI > 30 kg/m2) and no diabetes and in the STEP-HFpEF DM trial of adults with obesity-related HFpEF and diabetes, semaglutide 2.4 mg was superior to placebo for improvement of HF symptoms and physical function. For the current prespecified secondary analysis, researchers compared data from 570 women (277 in the treatment group) and 575 men (296 in the treatment group) from both trials to assess baseline characteristics and treatment effect of semaglutide vs. placebo by sex.
Participants had HF with left ventricular ejection fraction (LVEF) of at least 45%, a BMI of at least 30 kg/m2, a score of less than 90 points on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and 6-minute walking distance of at least 100 m. Participants were randomly assigned, 1:1, to once-weekly semaglutide 2.4 mg or placebo for 52 weeks.
The researchers compared men and women for the dual primary endpoints of change in KCCQ-CSS score and percentage change in body weight. Secondary endpoints were change in 6-minute walking distance, and a hierarchical composite endpoint of all-cause death, HF events, C-reactive protein level, and changes in KCCQ-CSS score and the walking distance challenge.
Nearly 90% of men and women were white, and the groups were similarly aged. At baseline, women had higher mean BMI (38.8 kg/m2 vs. 37.1 kg/m2; P .001) and higher LVEF (60% vs. 55%; P .001). Women were more likely to be classified as New York Heart Association class III-IV, and they had lower baseline mean KCCQ CSS (54.7 vs. 63; P < .001) and 6-minute walking distance (270.5 m vs. 322.1 m; P .001). Mean C-reactive protein level was higher for women than men (4.4 mg/L vs. 3 mg/L; P = .002). Women had lower comorbidity rates, such as atrial fibrillation (39.8% vs. 50.6%), coronary artery disease (31.8% vs. 47.3%) and diabetes (47.9% vs. 59.7%; P .001 for all) than men. Women were less likely to have been treated with an SGLT2 inhibitor (14.6% vs. 24%; P .001) or an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at baseline (75.1% vs. 81.9%; P = .004).
Results stratified by sex showed significantly greater weight loss in the semaglutide groups vs. placebo — adjusted mean difference of 9.6% for women and 7.2% for men (P = .006). Six-minute walking distance and the hierarchical composite endpoint were significantly improved for the semaglutide group vs. placebo, with similar improvements for women and men.
“The STEP-HFpEF trial marks the beginning of a new era in the management of the obesity phenotype of HFpEF — arguably the most prevalent form of HFpEF globally — by changing the conversation about the role of obesity in the development and progression of HFpEF from a ‘comorbidity’ to a root cause and treatment target,” Verma said.
Reference:
- Verma S, et al. J Am Coll Cardiol. 2024;doi:10.1016/j.jacc.2024.06.001.
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Verma S. Symposium – clinical implications of the STEP-HFpEF program and defining the next steps forward. Presented at: American Diabetes Association Scientific Sessions; June 21-24, 2024; Orlando.
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