Summary: In a prespecified echocardiography substudy of the STEP-HFpEF Program (491 of 1,145 participants, 43%), once-weekly semaglutide 2.4 mg versus placebo over 52 weeks attenuated left atrial remodeling (estimated mean difference in LA volume -6.13 mL; 95% CI -9.85 to -2.41; P=0.0013) and right ventricular enlargement, with modest diastolic improvements. No effect was seen on left ventricular mass or systolic function. These are imaging surrogate outcomes, not clinical endpoints.
PICO Summary
| Element | Detail |
|---|---|
| Population | 491 of 1,145 adults (43%) with obesity-related HFpEF (LVEF =45%, BMI =30) enrolled in the pooled STEP-HFpEF and STEP-HFpEF DM trials; prespecified echocardiography substudy; multinational, double-blind RCT. |
| Intervention | Once-weekly subcutaneous semaglutide 2.4 mg for 52 weeks (n=253). |
| Comparison | Matching placebo for 52 weeks (n=238). |
| Outcome | Primary substudy outcome (change in LA volume): EMD -6.13 mL; 95% CI -9.85 to -2.41; P=0.0013. RV end-diastolic area: EMD -1.99 cm2; 95% CI -3.60 to -0.38; P=0.016. RV end-systolic area: EMD -1.41 cm2; 95% CI -2.42 to -0.40; P=0.0064. E-wave velocity: EMD -5.63 cm/s; 95% CI -9.42 to -1.84; P=0.0037. E/A ratio: EMD -0.14; 95% CI -0.24 to -0.04; P=0.0075. E/e’ average: EMD -0.79; 95% CI -1.60 to 0.01; P=0.05 (borderline, CI crosses null). No significant effect on LV dimensions, mass, or systolic function. No ARR/NNT reported (imaging substudy, not event-driven). |
Semaglutide and cardiac remodeling in obesity-related HFpEF
RCT echo substudy · obesity-related HFpEF · 52 weeks
Over 52 weeks, semaglutide attenuated left atrial and right ventricular remodeling versus placebo. These are imaging surrogate outcomes, not clinical endpoints.
Expert Commentary
This prespecified echocardiography substudy of the STEP-HFpEF Program offers a mechanistic complement to the clinical benefits already reported for semaglutide in obesity-related HFpEF. The verdict is that semaglutide was associated with measurable attenuation of adverse left atrial and right ventricular remodeling and modest improvement in diastolic indices, with the primary substudy outcome of left atrial volume met convincingly. These signals are biologically coherent and lend plausibility to the symptomatic gains seen in the parent trials. The principal limitation is that imaging was available in only 43% of randomised participants, so the substudy is best read as hypothesis-supporting rather than definitive, and the endpoints are surrogate measures rather than hospitalisations or mortality. The E/e’ average was only borderline (P=0.05, confidence interval touching the null), and left ventricular mass and systolic function were unchanged, which tempers any claim of broad structural reversal. The trials were manufacturer-sponsored, with sponsor employees among the authors, so independent replication is reassuring to await. Can I use this with my patients? Yes, as supportive context when discussing why semaglutide may help a patient with obesity-related HFpEF, while being candid that this analysis measures cardiac structure on echocardiography, not outcomes that patients feel directly. Clinicians should anchor decisions to the symptomatic and weight endpoints of the main trials and treat these remodeling data as encouraging corroboration.
References
Solomon SD, Ostrominski JW, Wang X, et al. Effect of semaglutide on cardiac structure and function in patients with obesity-related heart failure. J Am Coll Cardiol. 2024;84(17):1587-1602. doi:10.1016/j.jacc.2024.08.021