Summary: In a prespecified secondary analysis of the pooled STEP-HFpEF and STEP-HFpEF DM trials (n=1,145), semaglutide 2.4 mg weekly reduced NT-proBNP at 52 weeks versus placebo (estimated treatment ratio 0.82; 95% CI 0.74-0.91; P=0.0002). Improvements in health status were larger in participants with higher baseline NT-proBNP, while weight loss was similar across NT-proBNP levels.
PICO Summary
| Element | Detail |
|---|---|
| Population | 1,145 adults with obesity-related heart failure with preserved ejection fraction (HFpEF), pooled from two double-blind, placebo-controlled, randomised trials (STEP-HFpEF and STEP-HFpEF DM); multinational, multicentre. Prespecified secondary analysis. |
| Intervention | Semaglutide 2.4 mg subcutaneously once weekly for 52 weeks. Per-arm n not reported in the abstract. |
| Comparison | Matching placebo once weekly for 52 weeks. Per-arm n not reported in the abstract. |
| Outcome | NT-proBNP at 52 weeks: estimated treatment ratio 0.82 (95% CI 0.74-0.91; P=0.0002), favouring semaglutide. KCCQ-CSS health-status gains increased with baseline NT-proBNP tertile (tertile 1: +4.5 points, 95% CI 0.8-8.2; tertile 2: +6.2, 95% CI 2.4-10.0; tertile 3: +11.9, 95% CI 8.1-15.7; P interaction=0.02; continuous P interaction=0.004). Weight loss consistent across NT-proBNP levels (P interaction=0.21). No event-driven ARR/NNT reported in this biomarker analysis. |
Semaglutide and NT-proBNP in HFpEF
Pooled RCT secondary analysis · obesity-related HFpEF · 52 weeks
Semaglutide 2.4 mg lowered NT-proBNP by an estimated 18% versus placebo at 52 weeks in obesity-related HFpEF, with larger health-status gains in patients with higher baseline NT-proBNP.
Expert Commentary
This prespecified secondary analysis adds mechanistic weight to the STEP-HFpEF programme by showing that semaglutide does more than mechanically unload an overweight heart. The 18 percent relative reduction in NT-proBNP, a randomised within-trial comparison, is consistent with a genuine effect on heart-failure pathobiology rather than a measurement artefact of weight change. The signal that health-status benefit tracks with baseline NT-proBNP is biologically coherent, since patients with higher peptide levels carry more congestion to relieve. Two cautions temper enthusiasm. First, the biomarker-by-subgroup interactions are exploratory and hypothesis-generating; they describe associations across tertiles and should not be read as proof that NT-proBNP can be used to select responders. Second, the programme was funded by the manufacturer of semaglutide and several authors are company employees, so independent replication of the NT-proBNP finding would strengthen confidence. Can I use this with my patients? Yes, for the symptomatic patient with obesity-related HFpEF who already meets STEP-HFpEF criteria, this analysis reassures that the drug acts on disease biology and that those with higher NT-proBNP may feel the most symptomatic benefit. It does not yet justify titrating therapy to a biomarker target. Future trials should test whether NT-proBNP-guided selection improves hard outcomes.
References
Petrie MC, Borlaug BA, Butler J, et al. Semaglutide and NT-proBNP in obesity-related HFpEF: insights from the STEP-HFpEF program. J Am Coll Cardiol. 2024;84(1):27-40. doi:10.1016/j.jacc.2024.04.022