Summary:
In 1,145 adults with obesity-related HFpEF (BMI ≥30, LVEF ≥45%, NYHA II-IV) pooled from STEP-HFpEF and STEP-HFpEF DM trials, semaglutide 2.4 mg subcutaneous weekly for 52 weeks significantly improved KCCQ-CSS (+7.5 points, P<0.0001), body weight (-8.4%, P<0.0001), 6MWD (+17.1m, P<0.0001), and CRP (-36%, P<0.0001) compared to matching placebo, with fewer serious adverse events (161 vs 301) and consistent benefits regardless of diabetes status.
| PICO | Description |
|---|---|
| Population | 1,145 adults with obesity-related HFpEF (BMI ≥30, LVEF ≥45%, NYHA II-IV) from pooled trials. |
| Intervention | Semaglutide 2.4 mg subcutaneous weekly for 52 weeks. |
| Comparison | Matching placebo weekly, double-blind. |
| Outcome | KCCQ +7.5, weight -8.4%, 6MWD +17.1m, CRP -36%. Fewer serious AEs (161 vs 301). |
STEP-HFpEF Pooled Analysis
Pooled RCT · obesity-HFpEF · 52 weeks
Semaglutide improved heart-failure symptoms and physical limitations, reduced bodyweight, and lowered inflammation in obesity-related HFpEF, with benefits consistent across subgroups and fewer serious adverse events than placebo.
Clinical Context
HFpEF is half of heart failure cases. The obesity-HFpEF phenotype causes volume overload, exercise intolerance, and systemic inflammation.
Clinical Pearls
1. Clinically Meaningful Symptom Improvement: KCCQ +7.5 exceeds 5-point threshold for clinical meaningfulness.
2. Functional Capacity Gain: 17m 6MWD improvement translates to better daily activities.
3. Anti-Inflammatory Effect: 36% CRP reduction addresses key pathophysiology.
4. Safety Signal: Fewer serious AEs with semaglutide (161 vs 301).
Practical Application
Consider semaglutide for obesity-related HFpEF regardless of diabetes status. Integrate with SGLT2i and appropriate diuresis.
Study Limitations
52-week follow-up. Hard outcomes not powered. BMI <30 excluded.
Bottom Line
Semaglutide significantly improves symptoms, function, weight, and inflammation in obesity-HFpEF regardless of diabetes status.
Source: Butler J, et al. “Semaglutide in Obesity-Related HFpEF: STEP-HFpEF Pooled Analysis.” Lancet. 2024. Read article