Semaglutide yields more weight loss in women with HF, improves symptoms

Semaglutide, originally developed for managing type 2 diabetes and obesity, has shown considerable promise in alleviating symptoms of a prevalent type of heart failure in both men and women, according to recent research. The medication, presented by Dr. Subodh Verma from St. Michael's Hospital, University of Toronto, at the American Diabetes Association's 2024 Scientific Sessions and published in the Journal of the American College of Cardiology, has revealed that women experience more significant weight loss while receiving the same symptomatic benefits as men.

The secondary analysis of the STEP-HFpEF (Semaglutide Treatment Effect in People with Obesity and HFpEF) program demonstrates that semaglutide offers benefits to both sexes that are not solely related to weight loss. This suggests the drug might have additional cardiovascular system effects independent of weight reduction. Over a 52-week period, the study compared semaglutide with a placebo in 1,145 participants, revealing notable sex differences.

This analysis aimed to determine if phenotypic features and the effects of semaglutide differ by sex in obesity-related heart failure with preserved ejection fraction (HFpEF). It evaluated sex-related influences on the disease's baseline characteristics and compared semaglutide's effects against a placebo on primary trial endpoints within the STEP-HFpEF program, which includes the STEP-HFpEF and STEP-HFpEF DM trials.

Dr. Mikhail Kosiborod, senior author of the study and a cardiologist at Saint Luke's Mid-America Heart Institute, emphasized the importance of understanding sex differences in obesity-related HFpEF. Kosiborod noted that obesity and visceral fat are critical factors in the development and progress of HFpEF, especially in women who represent a majority of those affected and who experience more severe symptoms and physical constraints due to the disease. The study highlights these differences and confirms the consistent benefits of semaglutide for both women and men.

Dr. Subodh Verma, the lead author, remarked that women with obesity and heart failure with preserved ejection fraction typically had higher BMI and were significantly more symptomatic at the study's start. Additionally, these women exhibited more systemic inflammation and were generally younger than those in previous HFpEF studies.

The study examined the effects of semaglutide 2.4 mg, administered once weekly, versus a placebo on the STEP-HFpEF program’s primary, confirmatory secondary, and exploratory outcomes by sex. The analysis included 1,145 participants with obesity-related HFpEF, of which 570 were women. Regardless of sex, semaglutide similarly improved heart failure-related symptoms, physical limitations, exercise capacity, and reduced inflammation and natriuretic peptides.

The improvements in heart failure symptoms and physical limitations were consistent across key subgroups, including age and BMI, in both men and women. Additionally, semaglutide lowered systolic blood pressure and waist circumference in participants. However, there were notable sex differences in weight reduction, with women experiencing greater weight loss than men (-9.6% vs. -7.2%).

At baseline, women had higher left ventricular ejection fraction, more severe symptoms, greater physical limitations, and higher inflammation levels than men. Despite having higher BMI, women had similar rates of hypertension and diuretic use but less atrial fibrillation compared to men. This may suggest that more women had a typical obesity phenotype of HFpEF, while men might have had left atrial myopathy HFpEF complicated by increased BMI.

In a related editorial, Dr. Anuradha Lala from the Mount Sinai School of Medicine highlighted the need for further studies to understand the mechanisms through which semaglutide provides benefits and to continue focusing on sex-specific differences in treatment responses.