ESC Congress 2026 Abstract · Oct 26, 2026

Semaglutide reduces volume overload and atrial remodelling in a novel experimental model of cardiometabolic HFpEF

By Thomas J, Bailey S, Nuon R et al.

Background: Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent cardiometabolic syndrome linked to obesity, type 2 diabetes, and hypertension. Recent trials, including STEP-HFpEF1 and SUMMIT2, demonstrate that glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve outcomes in obese HFpEF. However, as GLP-1RAs induce substantial weight loss, it remains unclear whether benefits reflect weight reduction alone or direct modification of HFpEF pathophysiology. Purpose: To determine whether semaglutide improves cardiac and systemic features of HFpEF in a novel preclinical model of obesity and volume overload. Methods: Male wild-type mice were fed a high-fat diet (HFD; 36% fat) for 16 weeks to induce obesity. Hypertension was induced at week 10 via uninephrectomy with deoxycorticosterone acetate (DOCA; 2.4 mg/day, s.c.) and 0.9% saline drinking water (1K/DOCA/salt). Semaglutide (0.04 mg/kg) or vehicle was administered every second day for 42 days. Blood pressure was measured by tail-cuff plethysmography, body composition by EchoMRI, and cardiac tissue analysed for histopathology and mRNA expression. Results: 1K/DOCA/salt + HFD increased blood pressure within 14 days compared with controls; semaglutide attenuated this rise (141 ± 10 vs. 120 ± 17 and 112 ± 14 mmHg; P < 0.05; n = 7–10). Free water content was elevated in 1K/DOCA/salt + HFD mice versus controls (0.37 ± 0.17 vs. 0.13 ± 0.06; P < 0.001) and tended to decrease with semaglutide (P = 0.059). Left atrial weight was increased in 1K/DOCA/salt + HFD mice (6.03 ± 0.23 vs. 4.14 ± 1.17 mg; P < 0.05) and reduced by semaglutide (5.56 ± 0.30 mg; P < 0.05). Conclusion: Semaglutide improved haemodynamic and structural features of cardiometabolic HFpEF, attenuating hypertension, volume expansion, and atrial remodelling. These findings support GLP-1 receptor agonism as a therapeutic strategy targeting systemic and cardiac drivers of HFpEF.J Thomas HFpEFFor image description, please refer to the figure legend and surrounding text.

doi.org/10.1093/eurheartj/ehag785.2983Open accessInterventions