Effects of semaglutide in obesity-related heart failure with preserved ejection fraction across the age spectrum: Findings from the STEP-HFpEF programme.

Pandey A, Moroney M, Verma S, Borlaug BA, Butler J, Davies MJ, Kitzman DW, Shah SJ, Petrie MC, Rönnbäck C, Domdey A, Rasmussen S, Chinnakondepalli KM, Patel S, Kosiborod MN

European journal of heart failure25 Nov 2025Cited by 2 (Europe PMC)

PMID41290376PMCIDPMC12765414DOI10.1002/ejhf.70049PepBankPUB-41290376

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Summary

BackgroundThe prevalence of heart failure with preserved ejection fraction (HFpEF) increases with age, and older adults with HFpEF have worse physical function, quality of life, and clinical outcomes. Semaglutide demonstrated efficacy in the treatment of obesity-related HFpEF in the STEP-HFpEF trials. Some have speculated that older patients may have less to gain from incretin therapies (and perhaps more to lose) than younger patients.AimsIn this pre-specified pooled subanalysis of the STEP-HFpEF trials, we evaluated the efficacy of semaglutide across the age spectrum.MethodsThe STEP-HFpEF and STEP-HFpEF DM trials enrolled participants with obesity-related HFpEF and randomized them to semaglutide 2.4 mg once weekly (n = 573) or placebo (n = 572) for 52 weeks. Dual primary outcomes (change in Kansas City Cardiomyopathy Questionnaire clinical summary score [KCCQ-CSS] and change in body weight) and secondary outcome measures (6-minute walk distance [6MWD], C-reactive protein, hierarchical composite endpoint containing all-cause death, heart failure events, changes in KCCQ-CSS and 6MWD) were compared across specific age groups; <55 years, 55-64 years, 65-74 years and ≥75 years.ResultsAmong 1145 randomized participants, 8.8% (N = 101) were <55, 23.3% (N = 267) were aged between 55-64, 42.4% (N = 485) were between 65-74, and 25.5% (N = 292) were 75 years or over. The efficacy of semaglutide on the dual primary endpoints was consistent across the age spectrum, KCCQ-CSS (p-interaction = 0.80), and body weight (p-interaction = 0.41). Similar benefits were observed for the key secondary endpoints, with no treatment effect heterogeneity across age groups. Moreover, the safety of semaglutide was consistent across age groups.ConclusionIn patients with HFpEF enrolled across the STEP-HFpEF and STEP-HFpEF DM trials, treatment with semaglutide improved disease-specific symptoms, physical function and reduced body weight across the age spectrum. The safety profile of semaglutide was consistent in older and younger patients.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. 4 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF, the effect of semaglutide on KCCQ-CSS did not differ across age groups.
In plain wordsIn adults with obesity-related heart failure, semaglutide worked similarly on symptoms in younger and older age groups.
Peptide
Semaglutide
Outcome
No significant changeKCCQ-CSS change by age group
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
p-interaction
0.8 NA
KCCQ-CSS by age
Source sentences
Summary
The efficacy of semaglutide on the dual primary endpoints was consistent across the age spectrum, KCCQ-CSS (p-interaction = 0.80)
2 context sentences(design, population, supporting numbers)
Summary · context
The STEP-HFpEF and STEP-HFpEF DM trials enrolled participants with obesity-related HFpEF and randomized them to semaglutide 2.4 mg once weekly (n = 573) or placebo (n = 572) for 52 weeks.
Summary · context
Among 1145 randomized participants, 8.8% (N = 101) were <55, 23.3% (N = 267) were aged between 55-64, 42.4% (N = 485) were between 65-74, and 25.5% (N = 292) were 75 years or over.
Show in the study text Report a problemFND-4129037601
02HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF, the effect of semaglutide on body weight did not differ across age groups.
In plain wordsIn adults with obesity-related heart failure, semaglutide led to similar weight change in younger and older age groups.
Peptide
Semaglutide
Outcome
No significant changeBody weight change by age group
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
p-interaction
0.41 NA
body weight by age
Source sentences
Summary
The efficacy of semaglutide on the dual primary endpoints was consistent across the age spectrum, KCCQ-CSS (p-interaction = 0.80), and body weight (p-interaction = 0.41)
2 context sentences(design, population, supporting numbers)
Summary · context
The STEP-HFpEF and STEP-HFpEF DM trials enrolled participants with obesity-related HFpEF and randomized them to semaglutide 2.4 mg once weekly (n = 573) or placebo (n = 572) for 52 weeks.
Summary · context
Among 1145 randomized participants, 8.8% (N = 101) were <55, 23.3% (N = 267) were aged between 55-64, 42.4% (N = 485) were between 65-74, and 25.5% (N = 292) were 75 years or over.
Show in the study text Report a problemFND-4129037602
03HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF, the key secondary endpoints showed similar benefits of semaglutide with no treatment effect heterogeneity across age groups.
In plain wordsIn adults with obesity-related heart failure, semaglutide gave similar secondary benefits in all age groups.
Peptide
Semaglutide
Outcome
No significant changeKey secondary endpoints by age group
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).
Source sentences
Summary
Similar benefits were observed for the key secondary endpoints, with no treatment effect heterogeneity across age groups.
2 context sentences(design, population, supporting numbers)
Summary · context
The STEP-HFpEF and STEP-HFpEF DM trials enrolled participants with obesity-related HFpEF and randomized them to semaglutide 2.4 mg once weekly (n = 573) or placebo (n = 572) for 52 weeks.
Summary · context
Among 1145 randomized participants, 8.8% (N = 101) were <55, 23.3% (N = 267) were aged between 55-64, 42.4% (N = 485) were between 65-74, and 25.5% (N = 292) were 75 years or over.
Show in the study text Report a problemFND-4129037603
04HumanRandomized controlled trialSafety outcome
In adults with obesity-related HFpEF, the safety of semaglutide was consistent across age groups.
In plain wordsIn adults with obesity-related heart failure, semaglutide safety looked similar in younger and older age groups.
Peptide
Semaglutide
Outcome
No significant changeSafety across age groups
Study
n = 1,145
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
2.4 mg once weekly · 52 weeksAs given in this study (human).
Source sentences
Summary
Moreover, the safety of semaglutide was consistent across age groups.
2 context sentences(design, population, supporting numbers)
Summary · context
The STEP-HFpEF and STEP-HFpEF DM trials enrolled participants with obesity-related HFpEF and randomized them to semaglutide 2.4 mg once weekly (n = 573) or placebo (n = 572) for 52 weeks.
Summary · context
Among 1145 randomized participants, 8.8% (N = 101) were <55, 23.3% (N = 267) were aged between 55-64, 42.4% (N = 485) were between 65-74, and 25.5% (N = 292) were 75 years or over.
Show in the study text Report a problemFND-4129037604

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Version history

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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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