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, Abildstrøm SZ, Davies MJ, Hovingh GK, Kitzman DW, Møller DV, Verma S, Einfeldt MN, Lindegaard ML and 20 more

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Rasmussen S, Abhayaratna W, Ahmed FZ, Ben-Gal T, Chopra V, Ezekowitz JA, Fu M, Ito H, Lelonek M, Melenovský V, Merkely B, Núñez J, Perna E, Schou M, Senni M, Sharma K, van der Meer P, Von Lewinski D, Wolf D, Kosiborod MN

Lancet (London, England)7 Apr 2024Cited by 296 (Europe PMC)

PMID38599221PMCIDPMC11317105DOI10.1016/s0140-6736(24)00469-0PepBankPUB-38599221

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study7

7 results from studies that gave the peptide. 7 results from people.

01HumanRandomized controlled trialEfficacy outcome
In people with obesity-related heart failure with preserved ejection fraction, semaglutide improved KCCQ-CSS more than placebo at week 52 (mean difference 7.5 points).
In plain wordsIn people with obesity and a type of heart failure, semaglutide improved symptoms and limits on activity more than placebo.
Peptide
Semaglutide
Outcome
IncreaseKCCQ-CSS change from baseline to week 52
Study
n = 1,145
Comparator
Placebo
Analysis
Primary
Outcome group
Heart function · Cardiovascular
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Measurements
Mean between-group difference in KCCQ-CSS
7.5 points
week 52
Source sentences
Summary
Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-g…
2 context sentences(design, population, supporting numbers)
Summary · context
We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries.
Summary · context
In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks.
Report a problemFND-3859922101
02HumanRandomized controlled trialEfficacy outcome
In people with obesity-related heart failure with preserved ejection fraction, semaglutide reduced bodyweight more than placebo at week 52 (mean difference -8.4%).
In plain wordsIn people with obesity and a type of heart failure, semaglutide lowered body weight more than placebo.
Peptide
Semaglutide
Outcome
DecreaseBodyweight change at week 52
Study
n = 1,145
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Measurements
Mean between-group difference in bodyweight
−8.4%
week 52
Source sentences
Summary
Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-g…
2 context sentences(design, population, supporting numbers)
Summary · context
We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries.
Summary · context
In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks.
Report a problemFND-3859922102
03HumanRandomized controlled trialEfficacy outcome
In people with obesity-related heart failure with preserved ejection fraction, semaglutide increased 6-min walk distance more than placebo at week 52 (mean difference 17.1 metres).
In plain wordsIn people with obesity and a type of heart failure, semaglutide improved walking distance more than placebo.
Peptide
Semaglutide
Outcome
Increase6-min walk distance at week 52
Study
n = 1,145
Comparator
Placebo
Analysis
Secondary
Outcome group
Exercise and physical function · Cardiovascular
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Measurements
Mean between-group difference in 6-min walk distance
17.1 metres
week 52
Source sentences
Summary
6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide gr…
2 context sentences(design, population, supporting numbers)
Summary · context
We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries.
Summary · context
In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks.
Report a problemFND-3859922103
04HumanRandomized controlled trialEfficacy outcome
In people with obesity-related heart failure with preserved ejection fraction, the hierarchical composite endpoint favoured semaglutide over placebo (win ratio 1.65).
In plain wordsIn people with obesity and a type of heart failure, a combined measure of death, heart failure events, symptoms and walking favoured semaglutide over placebo.
Peptide
Semaglutide
Outcome
IncreaseHierarchical composite endpoint
Study
n = 1,145
Comparator
Placebo
Analysis
Secondary
Outcome group
Heart function · Cardiovascular
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Measurements
Win ratio
1.65
hierarchical composite
Source sentences
Summary
6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide gr…
2 context sentences(design, population, supporting numbers)
Summary · context
We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries.
Summary · context
In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks.
Report a problemFND-3859922104
05HumanRandomized controlled trialEfficacy outcome
In people with obesity-related heart failure with preserved ejection fraction, semaglutide reduced CRP concentrations versus placebo (treatment ratio 0.64).
In plain wordsIn people with obesity and a type of heart failure, semaglutide lowered a blood marker of inflammation (CRP) more than placebo.
Peptide
Semaglutide
Outcome
DecreaseC-reactive protein concentration
Study
n = 1,145
Comparator
Placebo
Analysis
Secondary
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Measurements
CRP treatment ratio
0.64
semaglutide vs placebo
Source sentences
Summary
6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide gr…
2 context sentences(design, population, supporting numbers)
Summary · context
We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries.
Summary · context
In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks.
Report a problemFND-3859922105
06HumanRandomized controlled trialEfficacy outcome
In people with obesity-related heart failure with preserved ejection fraction, the efficacy of semaglutide on the dual primary endpoints was largely consistent across subgroups.
In plain wordsIn people with obesity and a type of heart failure, semaglutide worked in a similar way across age, race, sex, BMI and other groups.
Peptide
Semaglutide
Outcome
No significant changeConsistency of effect across subgroups
Study
n = 1,145
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Source sentences
Summary
For the dual primary endpoints, the efficacy of semaglutide was largely consistent across multiple subgroups, including those defined by age, race, sex, BMI, systolic blood pressure, baseline CRP, and left ventricular ejection fraction.
2 context sentences(design, population, supporting numbers)
Summary · context
We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries.
Summary · context
In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks.
Report a problemFND-3859922106
07HumanRandomized controlled trialSafety outcome
In people with obesity-related heart failure with preserved ejection fraction, 161 serious adverse events were reported with semaglutide compared with 301 with placebo.
In plain wordsIn people with obesity and a type of heart failure, fewer serious adverse events were reported with semaglutide than with placebo.
Peptide
Semaglutide
Outcome
DecreaseSerious adverse events
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Measurements
Serious adverse events
161 events
semaglutide
Serious adverse events
301 events
placebo
Source sentences
Summary
161 serious adverse events were reported in the semaglutide group compared with 301 in the placebo group.
1 context sentence(design, population, supporting numbers)
Summary · context
Overall, 1145 were included in our pooled analysis, 573 in the semaglutide group and 572 in the placebo group.
Report a problemFND-3859922107

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials2

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

2 trials · 2 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3NCT04916470

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

Novo Nordisk A/Sn = 61715 Jun 2021 to 11 Oct 2023

Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2

Trial page ClinicalTrials.govUpdated 26 Nov 2025

CompletedPhase 3Results postedNCT04788511

Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity

Novo Nordisk A/Sn = 52916 Mar 2021 to 18 Apr 2023

Obesity

Trial page ClinicalTrials.govUpdated 5 Dec 2025

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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Terms as the source lists them.

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