Phase 3 · Semaglutide

STEP HFpEF DM 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, and Type 2 Diabetes

Change in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score (Score on a scale), Baseline (week 0), end of treatment (week 52). Semaglutide 2.4 mg: 14.4; Placebo: 7.6.

Participants
617
Status
completed
Completed
2023-10-11
Sponsor
Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT04916470), updated at source Nov 2, 2026. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What STEP HFpEF DM measured first

Change in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary ScoreScore on a scale · Baseline (week 0), end of treatment (week 52) · mean
Semaglutide 2.4 mgn=281Placebon=272
14.4(18.3)7.6(18.8)
Percentage Change in Body WeightPercentage change in body weight · Baseline (week 0), end of treatment (week 52) · mean
Semaglutide 2.4 mgn=286Placebon=278
-10.2(6.8)-3.2(5.9)
Side effects by arm

Side effects in STEP HFpEF DM

Percent of participants affected, From baseline (week 0) to end of trial (week 57). The most common events the registry lists.

EventSemaglutide 2.4 mgPlacebo
Any serious event17.7%28.8%
Nausea17.7%5.9%
Diarrhoea13.5%6.5%
COVID-198.4%10.1%
Cardiac failure4.2%9.8%
Vomiting8.4%2.3%
Decreased appetite5.2%3.3%
Secondary outcomes

What else it measured

Change in Six-minute Walking DistanceMeters · Baseline (week 0), end of treatment (week 52) · mean
Semaglutide 2.4 mgn=281Placebon=265
16.9(54.3)3.8(49.8)
Hierarchical Composite Endpoint: Total Number of Wins for Each Treatment GroupNumber of wins · Baseline (week 0), end of trial (week 57) · number
MeasureSemaglutide 2.4 mgn=310Placebon=306
Time to all-cause death27961814
Number of heart failure events44341171
Time to first heart failure event3426
Change in KCCQ-CSS greater than or equal to (>=)15 point difference3061817303
Change in KCCQ-CSS >=10 point difference62504763
Change in KCCQ-CSS >=5 point difference69255912
Change in six minute walking distance (6MWD) >=30 metre difference46073920
Change in C-Reactive ProteinRatio to baseline of C-Reactive Protein · From baseline (week -2) to end of treatment (week 52) · geometric mean
Semaglutide 2.4 mgn=286Placebon=277
0.58(146.6)0.91(128.4)
Participants Achieving 10% Weight Loss or More (Yes/No)Participants · At Week 52 · count of participants
MeasureSemaglutide 2.4 mgn=286Placebon=278
Yes14729
No139249
Participants Achieving 15% Weight Loss or More (Yes/No)Participants · At Week 52 · count of participants
MeasureSemaglutide 2.4 mgn=286Placebon=278
Yes6411
No222267
Participants Achieving 20% Weight Loss or More (Yes/No)Participants · At Week 52 · count of participants
MeasureSemaglutide 2.4 mgn=286Placebon=278
Yes215
No265273
Participants Improving 5 Points or More in KCCQ Clinical Summary Score (Yes/No)Participants · At Week 52 · count of participants
MeasureSemaglutide 2.4 mgn=281Placebon=272
Yes205149
No76123
Participants Improving 10 Points or More in KCCQ Clinical Summary Score (Yes/No)Participants · At Week 52 · count of participants
MeasureSemaglutide 2.4 mgn=281Placebon=272
Yes163116
No118156
Change in KCCQ Overall Summary ScoreScore on a scale · Baseline (week 0), end of treatment (week 52) · mean
Semaglutide 2.4 mgn=281Placebon=272
14.4(18.1)7.6(18.6)
Participants Achieving Threshold for Clinically Meaningful Within-participant Change in KCCQ-CSS (PGI-S)Participants · At Week 52 · count of participants
Semaglutide 2.4 mgn=281Placebon=272
12083
Participants Achieving Threshold for Clinically Meaningful Within-participant Change in Six Minute Walking Distance (6MWD) (PGI-S)Participants · At Week 52 · count of participants
Semaglutide 2.4 mgn=281Placebon=265
148104
Change in Waist CircumferenceCentimetre (cm) · From baseline (week 0) to end of treatment (week 52) · mean
Semaglutide 2.4 mgn=284Placebon=277
-8.9(7.9)-2.4(7.2)
The trial

How STEP HFpEF DM was run

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.

  • Semaglutide 2.4 mg once weekly (OW): Participants will receive semaglutide injections for 52 weeks.
  • Semaglutide placebo OW: Participants will receive semaglutide placebo injections for 52 weeks.
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% at screening * Diagnosed with T2D greater than or equal to 90 days prior to the day of screening * HbA1c of below or equal to 10.0% as measured at the screening visit Exclusion Criteria: * A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Published papers

Papers from STEP HFpEF DM

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

GLPcompare is an informational data platform, not a medical provider or pharmacy. Nothing here is medical advice, a diagnosis, or a recommendation to start, stop, or change any treatment. Data is aggregated from public sources and can be incomplete or out of date. Always confirm with a licensed clinician and the current FDA label.