In 1,145 obese HFpEF patients, semaglutide consistently improved symptoms and weight regardless of baseline diuretic use, with especially pronounced benefits in patients on loop diuretics and a 17% reduction in loop diuretic dose vs a 2.4% increase on placebo.
17% diuretic dose reductionSemaglutide reduced loop diuretic doses by 17% while placebo patients needed 2.4% more, suggesting genuine improvement in fluid balance and cardiac function
What the researchers found
Weight loss consistent across diuretic groups (-6.9% to -8.8%, interaction P=0.39). KCCQ improvement greater in loop diuretic users (+9.3 vs +4.7 points, P=0.042). Loop diuretic dose decreased 17% with semaglutide vs +2.4% with placebo (P<0.0001). Semaglutide: OR 2.67 for dose reduction, OR 0.35 for dose increase. All secondary endpoints consistent across diuretic subgroups.
Why it matters
Diuretic reduction in heart failure is a meaningful clinical outcome — it suggests improved fluid balance and cardiac function, not just symptom masking. That semaglutide allows patients to reduce their diuretic doses while improving symptoms indicates genuine disease modification.
The numbers in context
1,145 patients pooled from STEP-HFpEF and STEP-HFpEF-DM. Published in European Heart Journal.
How the study worked
Prespecified pooled analysis of STEP-HFpEF and STEP-HFpEF-DM (n=1,145). Participants stratified by baseline diuretic use: no diuretic (n=220), non-loop only (n=223), loop ≤40 mg furosemide equivalents (n=174), loop >40 mg (n=528). Assessed efficacy endpoints and loop diuretic dose changes over 52 weeks.
Who was studied
Patients with obesity-related HFpEF from STEP-HFpEF and STEP-HFpEF-DM trials
What this study cannot tell us
Subgroup analysis — though prespecified, subgroup sizes vary. The diuretic dose reduction doesn't necessarily mean improved heart failure per se (could reflect weight-related fluid loss). Open-label nature of diuretic adjustments may introduce bias. 52-week follow-up may not capture long-term diuretic trajectory.
How to read the evidence
Rated strong: prespecified pooled analysis of two rigorous RCTs, published in European Heart Journal. Subgroup findings are consistent across endpoints.
When this study was published
Published in 2024 in European Heart Journal. Extends STEP-HFpEF evidence by demonstrating semaglutide benefits across the full spectrum of diuretic use.
The bigger picture
This analysis suggests semaglutide doesn't just improve HFpEF symptoms — it may alter the underlying disease trajectory, allowing patients to reduce the diuretic doses they depend on. For heart failure management, reducing medication burden while improving outcomes represents a true therapeutic advance.
Questions still open
- Could semaglutide eventually allow some HFpEF patients to discontinue diuretics entirely?
- Is the greater symptom benefit in loop diuretic users because these patients had more room for improvement?
- Does the diuretic dose reduction translate to fewer diuretic-related adverse effects (electrolyte abnormalities, kidney function)?
Common questions
Can semaglutide reduce the need for heart failure medications?
Does semaglutide work for heart failure patients already on diuretics?
Read the original research
Semaglutide and diuretic use in obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF-DM trials.
European heart journal, 45(35), 3254-3269
Citation
Shah, Sanjiv J; Sharma, Kavita; Borlaug, Barry A; Butler, Javed; Davies, Melanie; Kitzman, Dalane W; Petrie, Mark C; Verma, Subodh; Patel, Shachi; Chinnakondepalli, Khaja M; Einfeldt, Mette N; Jensen, Thomas J; Rasmussen, Søren; Asleh, Rabea; Ben-Gal, Tuvia; Kosiborod, Mikhail N. (2024). Semaglutide and diuretic use in obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF-DM trials.. European heart journal, 45(35), 3254-3269. https://doi.org/10.1093/eurheartj/ehae322