Atrial Fibrillation and Semaglutide Effects in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Program.

Verma S, Butler J, Borlaug BA, Davies MJ, Kitzman DW, Petrie MC, Shah SJ, Jensen TJ, Rasmussen S, Rönnbäck C, Merkely B, O'Keefe E, Kosiborod MN

Journal of the American College of Cardiology30 Aug 2024Cited by 36 (Europe PMC)

PMID39217565PMCIDPMC11486552DOI10.1016/j.jacc.2024.08.023PepBankPUB-39217565

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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: CC BY-NC-ND. Results still quote short attributed sentences.

Results from this study13

13 results from studies that gave the peptide. 13 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF, semaglutide consistently reduced body weight regardless of atrial fibrillation status (interaction P values not significant).
In plain wordsIn adults with obesity-related heart failure, semaglutide lowered body weight, with or without atrial fibrillation.
Peptide
Semaglutide
Outcome
DecreaseBody weight reduction regardless of AF status
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).
Source sentences
Summary
Semaglutide consistently reduced CRP, NT-proBNP, and body weight regardless of AF status (all P interaction values not significant).
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m², and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks.
Report a problemFND-3921756511
02HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF without atrial fibrillation, semaglutide improved the heart failure symptom score (KCCQ-CSS), by less than in those with atrial fibrillation.
In plain wordsIn adults with obesity-related heart failure without atrial fibrillation, semaglutide improved heart failure symptoms, but less than in people with atrial fibrillation.
Peptide
Semaglutide
Outcome
IncreaseKCCQ-CSS change in participants without atrial fibrillation
Study
n = 627
Comparator
Placebo
Analysis
Primary
Outcome group
Heart function · Cardiovascular
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Measurements
KCCQ-CSS difference
4.3 points
without AF
Source sentences
Summary
Semaglutide led to larger improvements in KCCQ-CSS (11.5 points [95% CI: 8.3-14.8] vs 4.3 points [95% CI: 1.3-7.2]; P interaction = 0.001) and the hierarchal composite endpoint (win ratio of 2.25 [95% CI: 1.79-2.83] vs 1.30 [95% CI: 1.06-1.59]; P interaction < 0.001) in participants with AF vs without AF, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m², and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks.
Report a problemFND-3921756502
03HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF and atrial fibrillation, semaglutide improved the heart failure symptom score (KCCQ-CSS), by more than in those without atrial fibrillation.
In plain wordsIn adults with obesity-related heart failure and atrial fibrillation, semaglutide improved heart failure symptoms, more than in people without atrial fibrillation.
Peptide
Semaglutide
Outcome
IncreaseKCCQ-CSS change in participants with atrial fibrillation
Study
n = 518
Comparator
Placebo
Analysis
Primary
Outcome group
Heart function · Cardiovascular
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Measurements
KCCQ-CSS difference
11.5 points
with AF
Source sentences
Summary
Semaglutide led to larger improvements in KCCQ-CSS (11.5 points [95% CI: 8.3-14.8] vs 4.3 points [95% CI: 1.3-7.2]; P interaction = 0.001) and the hierarchal composite endpoint (win ratio of 2.25 [95% CI: 1.79-2.83] vs 1.30 [95% CI: 1.06-1.59]; P interaction < 0.001) in participants with AF vs without AF, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m², and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks.
Report a problemFND-3921756501
04HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF, semaglutide consistently reduced CRP regardless of atrial fibrillation status (interaction P values not significant).
In plain wordsIn adults with obesity-related heart failure, semaglutide lowered the inflammation marker CRP, with or without atrial fibrillation.
Peptide
Semaglutide
Outcome
DecreaseCRP reduction regardless of AF status
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).
Source sentences
Summary
Semaglutide consistently reduced CRP, NT-proBNP, and body weight regardless of AF status (all P interaction values not significant).
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m², and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks.
Report a problemFND-3921756509
05HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF without atrial fibrillation, semaglutide improved the hierarchical composite endpoint, with a win ratio smaller than in those with atrial fibrillation.
In plain wordsIn adults with obesity-related heart failure without atrial fibrillation, semaglutide improved a combined heart score, but less than in people with atrial fibrillation.
Peptide
Semaglutide
Outcome
IncreaseHierarchical composite endpoint in participants without atrial fibrillation
Study
n = 627
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
1.3 ratio
without AF
Source sentences
Summary
Semaglutide led to larger improvements in KCCQ-CSS (11.5 points [95% CI: 8.3-14.8] vs 4.3 points [95% CI: 1.3-7.2]; P interaction = 0.001) and the hierarchal composite endpoint (win ratio of 2.25 [95% CI: 1.79-2.83] vs 1.30 [95% CI: 1.06-1.59]; P interaction < 0.001) in participants with AF vs without AF, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m², and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks.
Report a problemFND-3921756504
06HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF and atrial fibrillation, semaglutide improved the hierarchical composite endpoint, with a win ratio larger than in those without atrial fibrillation.
In plain wordsIn adults with obesity-related heart failure and atrial fibrillation, semaglutide improved a combined heart score, more than in people without atrial fibrillation.
Peptide
Semaglutide
Outcome
IncreaseHierarchical composite endpoint in participants with atrial fibrillation
Study
n = 518
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
2.25 ratio
with AF
Source sentences
Summary
Semaglutide led to larger improvements in KCCQ-CSS (11.5 points [95% CI: 8.3-14.8] vs 4.3 points [95% CI: 1.3-7.2]; P interaction = 0.001) and the hierarchal composite endpoint (win ratio of 2.25 [95% CI: 1.79-2.83] vs 1.30 [95% CI: 1.06-1.59]; P interaction < 0.001) in participants with AF vs without AF, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m², and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks.
Report a problemFND-3921756503
07HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF, semaglutide consistently reduced NT-proBNP regardless of atrial fibrillation status (interaction P values not significant).
In plain wordsIn adults with obesity-related heart failure, semaglutide lowered the heart strain marker NT-proBNP, with or without atrial fibrillation.
Peptide
Semaglutide
Outcome
DecreaseNT-proBNP reduction regardless of AF status
Study
n = 1,145
Comparator
Placebo
Analysis
Exploratory
Outcome group
Heart function · Cardiovascular
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Source sentences
Summary
Semaglutide consistently reduced CRP, NT-proBNP, and body weight regardless of AF status (all P interaction values not significant).
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m², and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks.
Report a problemFND-3921756510
08HumanRandomized controlled trialSafety outcome
There were fewer serious adverse events with semaglutide than with placebo irrespective of atrial fibrillation history.
In plain wordsSerious side effects were less frequent with semaglutide than with placebo, with or without atrial fibrillation.
Peptide
Semaglutide
Outcome
DecreaseSerious adverse events by AF history
Study
n = 1,145
Comparator
Placebo
Outcome group
Adverse events · Cardiovascular
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Source sentences
Summary
There were fewer serious adverse events and serious cardiac disorders in participants treated with semaglutide vs placebo
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m², and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks.
Report a problemFND-3921756512
09HumanRandomized controlled trialSafety outcome
There were fewer serious cardiac disorders with semaglutide than with placebo irrespective of atrial fibrillation history.
In plain wordsSerious heart problems were less frequent with semaglutide than with placebo, with or without atrial fibrillation.
Peptide
Semaglutide
Outcome
DecreaseSerious cardiac disorders by AF history
Study
n = 1,145
Comparator
Placebo
Outcome group
Adverse events · Cardiovascular
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Source sentences
Summary
There were fewer serious adverse events and serious cardiac disorders in participants treated with semaglutide vs placebo irrespective of AF history.
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m², and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks.
Report a problemFND-3921756513
10HumanRandomized controlled trialEfficacy outcome
The proportion of patients with a KCCQ-CSS improvement of at least 5 points, semaglutide versus placebo, was higher in those with than without atrial fibrillation (interaction P below 0.05).
In plain wordsThe gap between semaglutide and placebo in people with a symptom gain of at least 5 points was larger with atrial fibrillation than without.
Peptide
Semaglutide
Outcome
IncreaseResponders with at least 5-point KCCQ-CSS improvement by AF history
Study
n: not reported in source
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Source sentences
Summary
The proportions of patients receiving semaglutide vs those receiving placebo experiencing ≥5-, ≥10-, ≥15-, and ≥20-point improvement in KCCQ-CSS were also higher in those with (vs without) AF (all P interaction values <0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m², and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks.
Report a problemFND-3921756505
11HumanRandomized controlled trialEfficacy outcome
The proportion of patients with a KCCQ-CSS improvement of at least 10 points, semaglutide versus placebo, was higher in those with than without atrial fibrillation (interaction P below 0.05).
In plain wordsThe gap between semaglutide and placebo in people with a symptom gain of at least 10 points was larger with atrial fibrillation than without.
Peptide
Semaglutide
Outcome
IncreaseResponders with at least 10-point KCCQ-CSS improvement by AF history
Study
n: not reported in source
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Source sentences
Summary
The proportions of patients receiving semaglutide vs those receiving placebo experiencing ≥5-, ≥10-, ≥15-, and ≥20-point improvement in KCCQ-CSS were also higher in those with (vs without) AF (all P interaction values <0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m², and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks.
Report a problemFND-3921756506
12HumanRandomized controlled trialEfficacy outcome
The proportion of patients with a KCCQ-CSS improvement of at least 15 points, semaglutide versus placebo, was higher in those with than without atrial fibrillation (interaction P below 0.05).
In plain wordsThe gap between semaglutide and placebo in people with a symptom gain of at least 15 points was larger with atrial fibrillation than without.
Peptide
Semaglutide
Outcome
IncreaseResponders with at least 15-point KCCQ-CSS improvement by AF history
Study
n: not reported in source
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Source sentences
Summary
The proportions of patients receiving semaglutide vs those receiving placebo experiencing ≥5-, ≥10-, ≥15-, and ≥20-point improvement in KCCQ-CSS were also higher in those with (vs without) AF (all P interaction values <0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m², and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks.
Report a problemFND-3921756507
13HumanRandomized controlled trialEfficacy outcome
The proportion of patients with a KCCQ-CSS improvement of at least 20 points, semaglutide versus placebo, was higher in those with than without atrial fibrillation (interaction P below 0.05).
In plain wordsThe gap between semaglutide and placebo in people with a symptom gain of at least 20 points was larger with atrial fibrillation than without.
Peptide
Semaglutide
Outcome
IncreaseResponders with at least 20-point KCCQ-CSS improvement by AF history
Study
n: not reported in source
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Source sentences
Summary
The proportions of patients receiving semaglutide vs those receiving placebo experiencing ≥5-, ≥10-, ≥15-, and ≥20-point improvement in KCCQ-CSS were also higher in those with (vs without) AF (all P interaction values <0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m², and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks.
Report a problemFND-3921756508

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

Registered trials1

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

1 trial · 1 completed · 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

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

Subjects

Terms as the source lists them.

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