NCT04916470: STEP HFpEF DM

Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes

Completed Phase 3 Last updated 26 November 2025

What this trial tests

Phase 3 trial testing Semaglutide in Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2 in 617 participants. Completed in 11 October 2023.

Timeline

15 June 2021

Primary endpoint
11 October 2023

11 October 2023

Quick facts

Lead sponsor	Novo Nordisk A/S
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	617
Start date	15 June 2021
Primary completion	11 October 2023
Estimated completion	11 October 2023
Sites	180 locations across Italy, Japan, Netherlands, India, Austria, Sweden, United Kingdom, Germany

Drugs / interventions tested

• Semaglutide (semaglutide) — full drug profile →
• Placebo (Semaglutide)

Conditions studied

• Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2 — all drugs for Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2 →

Sponsor

Novo Nordisk A/S — full company profile →

Who can join

18 and older, any sex, with Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This study will look at how participants' daily life is affected by their heart failure. The study will also look at the change in participants' body weight.

This study will compare the effect of semaglutide (a new medicine) compared to "dummy" medicine on body weight and heart failure symptoms.

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 and physical activity.

The study will last for about 59 weeks, that is a little more than 1 year. Participants will have 12 clinic visits with the study doctor.

* At 6 of the visits participants will have blood samples taken.
* At 5 of the visits participants will be asked to fill in a questionnaire
* At 4 of the visits participants will have to do a 6-minute walking test
* At 3 of the visits participants will have a test to check the heart.
* participants will have their eyes checked before or at the start of the study and at the end of the study

Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.
   Kosiborod MN, Petrie MC, Borlaug BA, Butler J, et al · · 2024 · cited 476× · PMID 38587233 · DOI 10.1056/nejmoa2313917
2. Obesity and heart failure with preserved ejection fraction: new insights and pathophysiological targets.
   Borlaug BA, Jensen MD, Kitzman DW, Lam CSP, et al · · 2023 · cited 280× · PMID 35880317 · DOI 10.1093/cvr/cvac120
3. Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials.
   Butler J, Shah SJ, Petrie MC, Borlaug BA, et al · · 2024 · cited 234× · PMID 38599221 · DOI 10.1016/s0140-6736(24)00469-0
4. 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.
   Kosiborod MN, Deanfield J, Pratley R, Borlaug BA, et al · · 2024 · cited 203× · PMID 39222642 · DOI 10.1016/s0140-6736(24)01643-x
5. Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial.
   Borlaug BA, Kitzman DW, Davies MJ, Rasmussen S, et al · · 2023 · cited 159× · PMID 37635157 · DOI 10.1038/s41591-023-02526-x
6. Dapagliflozin for heart failure according to body mass index: the DELIVER trial.
   Adamson C, Kondo T, Jhund PS, de Boer RA, et al · · 2022 · cited 128× · PMID 36029309 · DOI 10.1093/eurheartj/ehac481
7. Heart Failure With Preserved Ejection Fraction: Heterogeneous Syndrome, Diverse Preclinical Models.
   Roh J, Hill JA, Singh A, Valero-Muñoz M, et al · · 2022 · cited 124× · PMID 35679364 · DOI 10.1161/circresaha.122.320257
8. Effect of Semaglutide on Cardiac Structure and Function in Patients With Obesity-Related Heart Failure.
   Solomon SD, Ostrominski JW, Wang X, Shah SJ, et al · · 2024 · cited 71× · PMID 39217567 · DOI 10.1016/j.jacc.2024.08.021