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Study · Randomized controlled trial · n = 1,145 · 2025

5 results

Frailty and Effects of Semaglutide in Obesity-Related HFpEF: Findings From the STEP-HFpEF Program.

Pandey A, Kitzman DW, Chinnakondepalli KM, Patel S, Borlaug BA, Butler J, Davies MJ, Shah SJ, Verma S, Rönnbäck C, Domdey A, Liisberg K and 6 more

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Schou M, Perna E, Ahmed FZ, Fu M, Petrie MC, Kosiborod MN

JACC. Heart failure15 Sept 2025Cited by 4 (Europe PMC)

PMID40956259 (opens in a new tab)DOI10.1016/j.jchf.2025.102610 (opens in a new tab)PepBankPUB-40956259
Publisher pagePubMedAsk about this study
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Summary

BackgroundFrailty is common in heart failure with preserved ejection fraction (HFpEF). In the STEP-HFpEF (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity) program, semaglutide improved heart failure (HF) symptoms and physical limitations and reduced body weight (BW) in participants with obesity-related HFpEF. Whether the efficacy and safety of semaglutide vary by frailty and the effects of semaglutide on frailty are unknown.ObjectivesThis study sought to evaluate the efficacy of semaglutide in participants with obesity-related HFpEF according to frailty status at baseline.MethodsThe authors performed a prespecified, pooled, participant-level analysis of the STEP-HFpEF program that included participants with obesity-related HFpEF. Participants were randomized to once-weekly semaglutide, 2.4 mg, or placebo for 52 weeks. Dual primary endpoints were changes in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) and BW. Frailty was estimated using a cumulative deficit-derived frailty index comprising 34 variables across multiple domains at baseline and follow-up. Efficacy and safety of semaglutide were evaluated in participants across 3 baseline frailty strata. Effects of semaglutide on frailty burden were also assessed.ResultsOf the 1,145 participants, 110 (9.6%) were nonfrail, 343 (30.0%) were more frail, and 692 (60.4%) were most frail. Semaglutide-mediated weight loss was similar across frailty strata (Pinteraction = 0.38). However, the effects of semaglutide on KCCQ-CSS varied by frailty status; participants who were most frail had the greatest improvement at 52 weeks (nonfrail mean difference: -1.5 [95% CI: -8.4 to 5.4]; more frail mean difference: 3.7 [95% CI: -0.2 to 7.6]; most frail mean difference: 11.0 [95% CI: 8.1-13.8]; Pinteraction < 0.001). Semaglutide reduced the burden of frailty during follow-up (OR for being nonfrail at 52 weeks: 3.16 [95% CI: 2.44-4.09]; P < 0.0001).ConclusionsSemaglutide resulted in a similar reduction in BW across frailty subgroups but greater improvements in HF-related symptoms. Moreover, semaglutide reduced frailty burden after 52 weeks of treatment. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF]; NCT04788511) (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP-HFpEF DM]; NCT04916470).
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

5 results from studies that gave the peptide. 5 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In adults with obesity-related HFpEF, semaglutide-mediated weight loss was similar across baseline frailty strata.

    In plain wordsIn adults with obesity-related heart failure, semaglutide's weight loss was similar whether people were not frail, more frail or most frail.

    Peptide
    Semaglutide
    Outcome
    No significant changeBody weight change by frailty stratum
    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-mediated weight loss was similar across frailty strata (Pinteraction = 0.38).
    1 context sentence
    Summary · context
    Participants were randomized to once-weekly semaglutide, 2.4 mg, or placebo for 52 weeks.
  2. 02HumanRandomized controlled trialEfficacy outcome

    In the most frail adults with obesity-related HFpEF, semaglutide improved KCCQ-CSS more than placebo at 52 weeks, with a significant interaction by frailty status.

    In plain wordsIn people with obesity-related heart failure who were most frail, semaglutide improved heart-failure symptom scores more than placebo did.

    Peptide
    Semaglutide
    Outcome
    IncreaseKCCQ-CSS at 52 weeks, most frail stratum
    Study

    n = 692

    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 mean difference
    11 points
    most frail

    Source sentences

    Summary
    However, the effects of semaglutide on KCCQ-CSS varied by frailty status; participants who were most frail had the greatest improvement at 52 weeks (nonfrail mean difference: -1.5 [95% CI: -8.4 to 5.4]; more frail mean difference: 3.7 [95% CI: -0.2 to 7.6]; most frail mean difference: 11.0 [95% CI: 8.1-13.8]
    1 context sentence
    Summary · context
    Participants were randomized to once-weekly semaglutide, 2.4 mg, or placebo for 52 weeks.
  3. 03HumanRandomized controlled trialEfficacy outcome

    In more frail adults with obesity-related HFpEF, semaglutide did not clearly change KCCQ-CSS versus placebo at 52 weeks.

    In plain wordsIn people with obesity-related heart failure who were more frail, semaglutide did not clearly change heart-failure symptom scores compared with placebo.

    Peptide
    Semaglutide
    Outcome
    No significant changeKCCQ-CSS at 52 weeks, more frail stratum
    Study

    n = 343

    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 mean difference
    3.7 points
    more frail

    Source sentences

    Summary
    more frail mean difference: 3.7 [95% CI: -0.2 to 7.6]
    1 context sentence
    Summary · context
    Participants were randomized to once-weekly semaglutide, 2.4 mg, or placebo for 52 weeks.
  4. 04HumanRandomized controlled trialEfficacy outcome

    In nonfrail adults with obesity-related HFpEF, semaglutide did not clearly change KCCQ-CSS versus placebo at 52 weeks.

    In plain wordsIn people with obesity-related heart failure who were not frail, semaglutide did not clearly change heart-failure symptom scores compared with placebo.

    Peptide
    Semaglutide
    Outcome
    No significant changeKCCQ-CSS at 52 weeks, nonfrail stratum
    Study

    n = 110

    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 mean difference
    −1.5 points
    nonfrail

    Source sentences

    Summary
    nonfrail mean difference: -1.5 [95% CI: -8.4 to 5.4]
    1 context sentence
    Summary · context
    Participants were randomized to once-weekly semaglutide, 2.4 mg, or placebo for 52 weeks.
  5. 05HumanRandomized controlled trialEfficacy outcome

    In adults with obesity-related HFpEF, semaglutide reduced the burden of frailty during follow-up, with higher odds of being nonfrail at 52 weeks versus placebo.

    In plain wordsIn adults with obesity-related heart failure, semaglutide reduced frailty over the year more than placebo did.

    Peptide
    Semaglutide
    Outcome
    DecreaseFrailty burden (nonfrail at 52 weeks)
    Study

    n = 1,145

    Comparator
    Placebo
    Outcome group
    Exercise and physical function · Whole body
    Studied dose
    2.4 mg once weekly · 52 weeksAs given in this study (human).

    Measurements

    OR for being nonfrail
    3.16 OR
    52 weeks

    Source sentences

    Summary
    Semaglutide reduced the burden of frailty during follow-up (OR for being nonfrail at 52 weeks: 3.16 [95% CI: 2.44-4.09]; P < 0.0001).
    1 context sentence
    Summary · context
    Participants were randomized to once-weekly semaglutide, 2.4 mg, or placebo for 52 weeks.

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 pageClinicalTrials.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.

  1. Version 2Current

    11 Oct 2026, 00:04 UTC

    Study results updated

  2. 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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