Primary outcome
What STEP-HFpEF measured first
| Semaglutide 2.4 mgn=243 | Placebon=237 |
|---|---|
| 16.8(17.9) | 10.3(17.3) |
| Semaglutide 2.4 mgn=246 | Placebon=242 |
|---|---|
| -13.9(8.1) | -2.5(5.6) |
Phase 3 · Semaglutide
STEP-HFpEF trial results
Effect of Semaglutide 2.4 mg Once Weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction
Change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) (Score on a scale), From baseline (week 0) to end of treatment (week 52). Semaglutide 2.4 mg: 16.8; Placebo: 10.3.
- Participants
- 529
- Status
- completed
- Completed
- 2023-04-18
- Sponsor
- Novo Nordisk A/S
As posted on ClinicalTrials.gov (NCT04788511), updated at source Dec 5, 2025. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.
Side effects by arm
Side effects in STEP-HFpEF
Percent of participants affected, From baseline (week 0) to end of trial (week 57). The most common events the registry lists.
| Event | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Any serious event | 13.3% | 26.7% |
| Nausea | 17.1% | 2.6% |
| COVID-19 | 13.7% | 15.4% |
| Diarrhoea | 9.1% | 3.8% |
| Constipation | 6.5% | 2.6% |
| Vomiting | 6.5% | 1.1% |
Secondary outcomes
What else it measured
| Semaglutide 2.4 mgn=240 | Placebon=225 |
|---|---|
| 23.5(59.2) | 5.8(62.7) |
| Semaglutide 2.4 mgn=263 | Placebon=266 |
|---|---|
| 60.1 | 34.9 |
| Semaglutide 2.4 mgn=241 | Placebon=243 |
|---|---|
| 0.55(121.5) | 0.92(105.3) |
| Measure | Semaglutide 2.4 mgn=246 | Placebon=242 |
|---|---|---|
| No | 34.1 | 90.5 |
| Yes | 65.9 | 9.5 |
| Measure | Semaglutide 2.4 mgn=246 | Placebon=242 |
|---|---|---|
| No | 56.1 | 97.9 |
| Yes | 43.9 | 2.1 |
| Measure | Semaglutide 2.4 mgn=246 | Placebon=242 |
|---|---|---|
| No | 76.4 | 99.6 |
| Yes | 23.6 | 0.4 |
| Measure | Semaglutide 2.4 mgn=243 | Placebon=237 |
|---|---|---|
| No | 24.7 | 36.3 |
| Yes | 75.3 | 63.7 |
| Measure | Semaglutide 2.4 mgn=243 | Placebon=237 |
|---|---|---|
| No | 36.6 | 51.5 |
| Yes | 63.4 | 48.5 |
| Semaglutide 2.4 mgn=243 | Placebon=237 |
|---|---|
| 16.8(18.3) | 10.9(17.5) |
| Semaglutide 2.4 mgn=243 | Placebon=237 |
|---|---|
| 43.2 | 32.5 |
| Semaglutide 2.4 mgn=240 | Placebon=225 |
|---|---|
| 42.5 | 28.0 |
| Semaglutide 2.4 mgn=246 | Placebon=243 |
|---|---|
| -6.4(19.0) | -1.1(17.5) |
The trial
How STEP-HFpEF was run
This study will look at how the participants daily life is affected by their heart failure. The study will also look at the change in participants body weight from the start to the end of the study. This is to compare the effect on heart failure symptoms and on body weight in people taking semaglutide (a new medicine) to people taking "dummy" medicine. Participants will either get semaglutide or "dummy" medicine - which treatment participants get is decided by chance. Participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skin fold in the stomach area, thigh or upper arm. During the study participants will have talks with the study staff about healthy lifestyle choices including healthy food and physical activity. The study will last for approximately 59 weeks. Participants will have 11 clinic visits and 1 phone call with the study doctor. Women: Women cannot take part if they are pregnant, breast-feeding or plan to become pregnant during the study period.
- Semaglutide: All participants will receive either semaglutide 2.4 mg once weekly or placebo once weekly as add-on to standard of care. During the first 16 weeks, the dose of semaglutide or placebo will be gradually escalated from 0.25 mg once weekly until target dose.
- Placebo (semaglutide): All participants will receive either semaglutide 2.4 mg once weekly or placebo once weekly as add-on to standard of care. During the first 16 weeks, the dose of semaglutide or placebo will be gradually escalated from 0.25 mg once weekly until target dose.
Who could join the trial
Inclusion Criteria: * Male or female, age above or equal to 18 years at the time of signing informed consent. * Body mass index (BMI) greater than or equal to 30.0 kg/m\^2 * New York Heart Association (NYHA) Class II-IV * Left ventricular ejection fraction (LVEF) greater than or equal to 45 percentage at screening Exclusion Criteria: * A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records * Haemoglobin A1c (HbA1c) greater than or equal to 6.5 percentage (48 mmol/mol) based on latest available value from medical records, no older than 3 months or if unavailable a local measurement at screening
Published papers
Papers from STEP-HFpEF
- Kosiborod MN, Abildstrom SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, Hovingh GK, Kitzman DW, Lindegaard ML, Moller DV, Shah SJ, Treppendahl MB, Verma S, Abhayaratna W, Ahmed FZ, Chopra V, Ezekowitz J, Fu M, Ito H, Lelonek M, Melenovsky V, Merkely B, Nunez J, Perna E, Schou M, Senni M, Sharma K, Van der Meer P, von Lewinski D, Wolf D, Petrie MC; STEP-HFpEF Trial Committees and Investigators. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J...
- Borlaug BA, Kitzman DW, Davies MJ, Rasmussen S, Barros E, Butler J, Einfeldt MN, Hovingh GK, Moller DV, Petrie MC, Shah SJ, Verma S, Abhayaratna W, Ahmed FZ, Chopra V, Ezekowitz J, Fu M, Ito H, Lelonek M, Melenovsky V, Nunez J, Perna E, Schou M, Senni M, van der Meer P, Von Lewinski D, Wolf D, Kosiborod MN. Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial. Nat Med. 2023 Sep;29(9):2358-2365. doi: 10.1038/s41591-023-02526-x....
- Kosiborod MN, Deanfield J, Pratley R, Borlaug BA, Butler J, Davies MJ, Emerson SS, Kahn SE, Kitzman DW, Lingvay I, Mahaffey KW, Petrie MC, Plutzky J, Rasmussen S, Ronnback C, Shah SJ, Verma S, Weeke PE, Lincoff AM; SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM Trial Committees and Investigators. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. Lancet....
- Shah SJ, Sharma K, Borlaug BA, Butler J, Davies M, Kitzman DW, Petrie MC, Verma S, Patel S, Chinnakondepalli KM, Einfeldt MN, Jensen TJ, Rasmussen S, Asleh R, Ben-Gal T, Kosiborod MN. 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. Eur Heart J. 2024 Sep 14;45(35):3254-3269. doi: 10.1093/eurheartj/ehae322.
- Butler J, Shah SJ, Petrie MC, Borlaug BA, Abildstrom SZ, Davies MJ, Hovingh GK, Kitzman DW, Moller DV, Verma S, Einfeldt MN, Lindegaard ML, Rasmussen S, Abhayaratna W, Ahmed FZ, Ben-Gal T, Chopra V, Ezekowitz JA, Fu M, Ito H, Lelonek M, Melenovsky V, Merkely B, Nunez J, Perna E, Schou M, Senni M, Sharma K, van der Meer P, Von Lewinski D, Wolf D, Kosiborod MN; STEP-HFpEF Trial Committees and Investigators. Semaglutide versus placebo in people with obesity-related heart failure with preserved...
- Butler J, Abildstrom SZ, Borlaug BA, Davies MJ, Kitzman DW, Petrie MC, Shah SJ, Verma S, Abhayaratna WP, Chopra V, Ezekowitz JA, Fu M, Ito H, Lelonek M, Nunez J, Perna E, Schou M, Senni M, van der Meer P, von Lewinski D, Wolf D, Altschul RL, Rasmussen S, Kosiborod MN. Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction. J Am Coll Cardiol. 2023 Nov 28;82(22):2087-2096. doi: 10.1016/j.jacc.2023.09.811. Epub 2023 Oct 8.
- Kosiborod MN, Verma S, Borlaug BA, Butler J, Davies MJ, Jon Jensen T, Rasmussen S, Erlang Marstrand P, Petrie MC, Shah SJ, Ito H, Schou M, Melenovsky V, Abhayaratna W, Kitzman DW; STEP-HFpEF Trial Committees and Investigators. Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity: A Prespecified Analysis of the STEP-HFpEF Trial. Circulation. 2024 Jan 16;149(3):204-216. doi: 10.1161/CIRCULATIONAHA.123.067505....
Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.
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