Published on Jun 26, 2024, in The Journal of the American College of Cardiology
A recent study has shown that women tend to lose more body weight on average when treated with semaglutide compared to men. This secondary analysis of the STEP-HFpEF (Semaglutide Treatment Effect in People with Obesity and Heart Failure with Preserved Ejection Fraction) program included individuals with diabetes mellitus (STEP-HFpEF DM) and was stratified by biological sex.
Background
Obesity-related heart failure with preserved ejection fraction (HFpEF) is a significant global health issue, particularly affecting women. HFpEF, caused by local and systemic changes, leads to severe symptoms, reduced functional status, and poorer clinical outcomes. Biological sex influences heart failure risk factors, clinical presentation, treatment responses, and prognosis. Women with HFpEF generally have better survival rates and fewer hospitalizations. However, the underlying differences in ventricular structure, function, body composition, and adiposity distribution between sexes may contribute to more severe clinical symptoms in women.
Study Details
The study aimed to analyze the impact of biological sex on various parameters, including anthropometric, cardiovascular health, inflammatory markers, and the effects of semaglutide therapy. Participants were recruited from 129 locations across 18 countries in Europe, Asia, and the Americas. They were randomized in a 1:1 ratio to receive either 2.40 mg of semaglutide or a placebo once weekly for 52 weeks. Eligible participants had HFpEF with a left ventricular ejection fraction (LVEF) of ≥45%, a body mass index (BMI) of ≥30 kg/m², and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) below 90 points.
Exclusions included previous or planned bariatric surgery, significant recent weight change, elevated systolic blood pressures, and severe diabetic maculopathy or retinopathy for STEP-HFpEF DM participants.
Primary outcomes were changes in body weight and KCCQ-CSS scores. Secondary outcomes included changes in six-minute walking distance (6MWD), a composite outcome of all-cause mortality, heart failure events, and C-reactive protein (CRP) levels. Exploratory outcomes included changes in waist circumference, systolic blood pressure, and NT-proBNP levels.
Results
Out of 1,145 participants (529 from STEP-HFpEF and 616 from STEP-HFpEF DM), 570 were female. Females had higher LVEF, BMI, CRP levels, physical limitations, and worse heart failure symptoms than males. They were less likely to have a history of coronary heart disease or atrial fibrillation and less likely to use sodium-glucose cotransporter-2 inhibitors (SGLT2i), ACE inhibitors, or angiotensin II receptor blockers (ARB). Baseline 6MWD and KCCQ-CSS scores were lower among females.
Semaglutide treatment improved KCCQ-CSS scores similarly in both sexes but led to greater weight loss in females (9.6%) compared to males (7.2%). The treatment also improved the composite outcome, 6MWD, and exploratory outcomes in both genders. Fewer serious adverse events were reported by semaglutide recipients compared to placebo recipients, though gastrointestinal issues and serious adverse events leading to drug discontinuation were similar between groups.
Conclusion
The study concluded that semaglutide treatment resulted in more significant weight loss in women with obesity-associated HFpEF. Regardless of gender, semaglutide improved heart failure symptoms, exercise capacity, physical limitations, inflammation, and natriuretic peptide levels. It was well tolerated, with fewer major side effects than the placebo in both sexes.
The findings underscore the importance of aggressive therapy in women with obesity-related HFpEF due to their higher total adiposity, inflammation, symptom intensity, and activity restriction. Further research on incretin-based treatments to reduce clinical events in obesity-related HFpEF is necessary.
Journal Reference
Subodh Verma et al., Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure with Preserved Ejection Fraction, JACC 2024, ISSN 0735-1097, DOI: 10.1016/j.jacc.2024.06.001