Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has shown promise in treating obesity-related heart failure with preserved ejection fraction (HFpEF), according to results from the SELECT trial presented at the European Society of Cardiology (ESC) Congress 2024. The trial evaluated semaglutide's efficacy in patients with HFpEF and has broader implications for its use in cardiovascular and metabolic diseases.
SELECT Trial Details
The SELECT trial involved two arms: one receiving semaglutide and the other a placebo, both as adjuncts to standard-of-care treatment. The semaglutide arm started with a once-weekly dose of 0.24mg, escalating every four weeks to a maintenance dose of 2.4mg. Semaglutide was administered via subcutaneous injection once per week. The primary focus was to assess the impact on cardiovascular outcomes in this patient population.
Key Findings on Efficacy
Trial results indicated that overweight or obese females with atherosclerotic cardiovascular disease (ASCVD), but without diabetes, experienced a lower risk of major adverse cardiovascular events (MACEs) compared to males. This was observed despite females having comparable age, blood pressure, and hemoglobin A1C (HbA1c), but higher low-density lipoprotein cholesterol (LDL-C), high-sensitivity C-reactive protein (hsCRP), and body mass index (BMI). Semaglutide also led to more significant reductions in body weight, waist circumference, and hsCRP in females than in males.
While the absolute risk reduction (ARR) was higher in males, the efficacy of semaglutide remained consistent across sexes regarding cardiovascular, metabolic, and kidney endpoints, irrespective of factors like myocardial infarction (MI) history, BMI, HbA1c, hsCRP, or estimated glomerular filtration rate (eGFR).
Safety Profile
The safety profile of semaglutide 2.4mg showed that fewer females receiving semaglutide experienced serious adverse events (SAEs) and adverse events (AEs) necessitating treatment discontinuation. However, the incidence of gastrointestinal (GI) AEs was comparable between males and females.
Expert Commentary
Dr. Subodh Verma, professor at the University of Toronto, highlighted these findings, noting the potential of semaglutide in addressing obesity-related HFpEF. Key opinion leaders (KOLs) interviewed by GlobalData emphasized that while semaglutide aids in type 2 diabetes (T2D) management and offers weight loss benefits, overall patient health remains paramount, underscoring the significance of cardiovascular outcome studies.
Market and Clinical Implications
Semaglutide is under pre-registration for HFpEF and is also being explored for chronic kidney disease (CKD), peripheral artery disease (PAD), peripheral vascular disease (PVD), and acute ischemic stroke. According to GlobalData’s Pharma Intelligence Center, there are multiple candidates in Phase III, II, and I clinical trials for HFpEF and obesity globally, indicating a robust pipeline aimed at addressing these conditions. Semaglutide's promising results position it as a potential long-awaited treatment for HFpEF patients, filling a significant gap in current therapeutic options.
