Summary: In the STEP-HFpEF DM randomised trial of 616 adults with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, once-weekly semaglutide 2.4 mg over 52 weeks improved symptoms and physical limitations (KCCQ-CSS difference 7.3 points, 95% CI 4.1 to 10.4) and reduced body weight (difference -6.4 percentage points, 95% CI -7.6 to -5.2) compared with placebo. Both primary end points favoured semaglutide (P<0.001).
PICO Summary
| Element | Detail |
|---|---|
| Population | 616 adults with heart failure with preserved ejection fraction (LVEF ≥45%), body-mass index ≥30, and type 2 diabetes; double-blind, placebo-controlled randomised trial conducted across multiple countries (STEP-HFpEF DM). |
| Intervention | Once-weekly subcutaneous semaglutide 2.4 mg for 52 weeks (n=310). |
| Comparison | Matching once-weekly placebo for 52 weeks (n=306); both arms continued background care. |
| Outcome | Co-primary end points: change in KCCQ-CSS +13.7 with semaglutide vs +6.4 with placebo (estimated difference 7.3 points; 95% CI 4.1 to 10.4; P<0.001); body-weight change -9.8% vs -3.4% (estimated difference -6.4 percentage points; 95% CI -7.6 to -5.2; P<0.001). Secondary: 6-minute walk distance +14.3 m (95% CI 3.7 to 24.9; P=0.008); hierarchical composite win ratio 1.58 (95% CI 1.29 to 1.94; P<0.001); CRP treatment ratio 0.67 (95% CI 0.55 to 0.80; P<0.001). Serious adverse events occurred in 17.7% (semaglutide) vs 28.8% (placebo). No absolute risk reduction or NNT reported for hard clinical events, which the trial was not powered to assess. |
Semaglutide in obesity-related HFpEF with diabetes
RCT · HFpEF + type 2 diabetes · 52 weeks
Over 52 weeks, semaglutide 2.4 mg produced greater weight loss and larger symptom and functional gains than placebo in obese, diabetic HFpEF. The trial was not powered for hard clinical events.
Expert Commentary
This trial provides moderate-quality evidence that semaglutide 2.4 mg meaningfully improves patient-reported symptoms, weight, and exercise capacity in obese, diabetic patients with HFpEF, a phenotype for which disease-modifying options have been limited. The KCCQ-CSS gain exceeds the threshold generally regarded as clinically important, and the reduction in serious adverse events, driven largely by fewer cardiac events, is reassuring rather than concerning. The principal limitation is that the trial was designed around symptom and functional surrogates over one year and was not powered for hard outcomes such as heart-failure hospitalisation or mortality; the favourable win ratio is encouraging but cannot establish event reduction. The open-label nature of weight loss makes complete blinding of subjective scores difficult, and the study was funded by the manufacturer, with several authors employed by the sponsor, so independent replication remains valuable. Can I use this with my patients? Yes, for the specific patient in front of you who has type 2 diabetes, a body-mass index of 30 or more, and symptomatic HFpEF, semaglutide is a reasonable evidence-based addition to guideline-directed therapy, provided gastrointestinal tolerability and cost are discussed. Longer-term outcome data and pragmatic effectiveness studies should now confirm whether these symptomatic gains translate into reduced hospitalisations.
References
Kosiborod MN, Petrie MC, Borlaug BA, et al. Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes. N Engl J Med. 2024;390(15):1394-1407. doi:10.1056/NEJMoa2313917