A review of recent studies shows that drugs like tirzepatide, which are already used for diabetes and weight loss, also help people with a type of heart failure (HFpEF) who are overweight. They cut body weight, lower inflammation markers, and improve heart stress signals, leading to better walking ability and quality of life, no matter how heavy the person is.

Heart failure with preserved ejection fraction (HFpEF) is associated with obesity, inflammation, and cardiac metabolism. While obesity contributes to HFpEF, the 'obesity paradox' suggests that higher BMI may correlate with better outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have cardiovascular benefits through weight loss, anti-inflammatory effects, and improved myocardial function. This systematic review involved randomized trials and cohort studies from 2015 to 2024, assessing GLP-1 RAs in patients with obese HFpEF (BMI ≥ 30 kg/m²). Outcomes included heart failure hospitalizations, mortality, exercise capacity, and quality of life. Eighteen studies involved over 22 000 participants. GLP-1 RAs, especially semaglutide and tirzepatide, consistently reduced weight, inflammation (C-reactive protein), and myocardial stress (N-terminal pro B-type natriuretic peptide) while improving 6-min walk distance and Kansas City Cardiomyopathy Questionnaire scores, uniformly across BMI groups. GLP-1 RAs counter the metabolic burden of obesity in HFpEF while preserving hemodynamic benefits, offering a promising therapeutic option.