AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Weight-Loss-Enriched Reverse Cardiac Remodeling After Semaglutide and Tirzepatide Initiation on Longitudinal Echocardiography
By Rajendran P, Saha G, Krishnappa P et al.
Background: Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptor agonists (GLP-1/GIP-RAs) are associated with a reduction in adverse cardiovascular events in patients with obesity and cardiovascular disease, but the underlying cardiac structural changes remain incompletely understood. Methods: Using de-identified electronic health records from the nference Federated Analytics Platform, we evaluated whether GLP-1/GIP-RAs are associated with cardiac remodeling via longitudinal echocardiography and whether this effect correlates with weight loss magnitude. Patients on semaglutide or tirzepatide with weight measurements and echocardiograms at baseline (0-2 years pre-prescription) and during follow-up (6 months to 4 years post-prescription) were stratified by weight loss within the first year: super-responders (>15%), moderate-responders (5-15%), and minimal-responders (<5%). A control cohort prescribed alternative weight-loss medications (benzphetamine, bupropion/naltrexone, diethylpropion, lorcaserin, orlistat, phendimetrazine, phentermine, phentermine/topiramate, and setmelanotide) was propensity-matched on age, sex, and baseline body mass index with semaglutide and tirzepatide patients. Longitudinal echocardiographic parameters (left atrial size, left ventricular (LV) size and function, and right ventricular (RV) function) were compared within and across groups using pre- vs. post-treatment paired analyses. Results: A total of 3,500 patients on semaglutide or tirzepatide with longitudinal echocardiograms were identified: 422 weight-loss super-responders (mean (standard deviation): 18.9 (11.4) kg), 1,426 moderate-responders (10.3 (9.5) kg), and 1,652 minimal-responders (4.7 (10.2) kg). Super-responders demonstrated a significant decrease in interventricular septal thickness, LV posterior wall thickness, LV end-diastolic diameter, RV systolic pressure (RVSP), and tricuspid regurgitation maximum velocity (TR Vmax) with semaglutide or tirzepatide treatment, with a small effect size (Table 1). Similar trends were observed in moderate- and minimal-responders, though effect sizes were negligible. Compared to propensity-matched controls, the super- and moderate-responders showed significantly greater decreases and larger effect sizes for septal thickness, posterior wall thickness, and RVSP (Table 2). Conclusions: Semaglutide and tirzepatide treatment were associated with favorable LV remodeling and lower RVSP and TR Vmax in a weight-loss-enriched manner, exceeding changes observed with alternative weight-loss medications.