Skip to content

Study · Randomized controlled trial · n = 1,145 · 2024

9 results

Semaglutide and diuretic use in obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF-DM trials.

Shah SJ, Sharma K, Borlaug BA, Butler J, Davies M, Kitzman DW, Petrie MC, Verma S, Patel S, Chinnakondepalli KM, Einfeldt MN, Jensen TJ and 4 more

Show all authors

Rasmussen S, Asleh R, Ben-Gal T, Kosiborod MN

European heart journal1 Sept 2024Cited by 68 (Europe PMC)

PMID38739118 (opens in a new tab)PMCIDPMC11400859 (opens in a new tab)DOI10.1093/eurheartj/ehae322 (opens in a new tab)PepBankPUB-38739118
Download PDFPubMedAsk about this study
Jump to 9 results

Summary

Background and aimsIn the STEP-HFpEF trial programme, treatment with semaglutide resulted in multiple beneficial effects in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Efficacy may vary according to baseline diuretic use, and semaglutide treatment could modify diuretic dose.MethodsIn this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks, we examined whether efficacy and safety endpoints differed by baseline diuretic use, as well as the effect of semaglutide on loop diuretic use and dose changes over the 52-week treatment period.ResultsAt baseline, across no diuretic (n = 220), non-loop diuretic only (n = 223), and loop diuretic [40 (n = 174) mg/day furosemide equivalents] groups, there was progressively higher prevalence of hypertension and atrial fibrillation; and greater severity of obesity and heart failure. Over 52 weeks of treatment, semaglutide had a consistent beneficial effect on change in body weight across diuretic use categories (adjusted mean difference vs. placebo ranged from -8.8% [95% confidence interval (CI) -10.3, -6.3] to -6.9% [95% CI -9.1, -4.7] from no diuretics to the highest loop diuretic dose category; interaction P = .39). Kansas City Cardiomyopathy Questionnaire clinical summary score improvement was greater in patients on loop diuretics compared to those not on loop diuretics (adjusted mean difference vs. placebo: +9.3 [6.5; 12.1] vs. +4.7 points [1.3, 8.2]; P = .042). Semaglutide had consistent beneficial effects on all secondary efficacy endpoints (including 6 min walk distance) across diuretic subgroups (interaction P = .24-.92). Safety also favoured semaglutide vs. placebo across the diuretic subgroups. From baseline to 52 weeks, loop diuretic dose decreased by 17% in the semaglutide group vs. a 2.4% increase in the placebo group (P < .0001). Semaglutide (vs. placebo) was more likely to result in loop diuretic dose reduction (odds ratio [OR] 2.67 [95% CI 1.70, 4.18]) and less likely dose increase (OR 0.35 [95% CI 0.23, 0.53]; P < .001 for both) from baseline to 52 weeks.ConclusionsIn patients with obesity-related HFpEF, semaglutide improved heart failure-related symptoms and physical limitations across diuretic use subgroups, with more pronounced benefits among patients receiving loop diuretics at baseline. Reductions in weight and improvements in exercise function with semaglutide vs. placebo were consistent in all diuretic use categories. Semaglutide also led to a reduction in loop diuretic use and dose between baseline and 52 weeks.Clinical trial registrationNCT04788511 and NCT04916470.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

9 results from studies that gave the peptide. 9 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    Semaglutide had consistent beneficial effects on all secondary efficacy endpoints, including 6 min walk distance, across diuretic subgroups (interaction P = .24-.92).

    In plain wordsIn heart failure with obesity, semaglutide helped secondary outcomes such as walking distance whatever the diuretic use.

    Peptide
    Semaglutide
    Outcome
    IncreaseSecondary efficacy endpoints including 6 min walk distance
    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
    Semaglutide had consistent beneficial effects on all secondary efficacy endpoints (including 6 min walk distance) across diuretic subgroups (interaction P = .24-.92).
    1 context sentence
    Summary · context
    In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks
  2. 02HumanRandomized controlled trialEfficacy outcome

    In obesity-related HFpEF, semaglutide reduced body weight versus placebo consistently across diuretic use categories (adjusted mean difference -8.8% to -6.9%; interaction P = .39).

    In plain wordsIn people with obesity and heart failure, semaglutide cut body weight more than placebo whatever their diuretic use.

    Peptide
    Semaglutide
    Outcome
    DecreaseBody weight change by baseline diuretic use
    Study

    n = 1,145

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    2.4 mg once weekly · 52 weeksAs given in this study (human).

    Measurements

    Adjusted mean difference vs placebo
    −8.8%
    no diuretics
    Adjusted mean difference vs placebo
    −6.9%
    highest loop diuretic dose

    Source sentences

    Summary
    Over 52 weeks of treatment, semaglutide had a consistent beneficial effect on change in body weight across diuretic use categories (adjusted mean difference vs. placebo ranged from -8.8% [95% confidence interval (CI) -10.3, -6.3] to -6.9% [95% CI -9.1, -4.7] from no diuretics to the highest loop diuretic dose category; interaction P = .39).
    1 context sentence
    Summary · context
    In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks
  3. 03HumanRandomized controlled trialEfficacy outcome

    The KCCQ clinical summary score improvement with semaglutide was greater in patients on loop diuretics than in those not on loop diuretics (P = .042).

    In plain wordsSemaglutide improved heart failure symptom scores more in people on loop diuretics than in people not taking them.

    Peptide
    Semaglutide
    Outcome
    IncreaseKCCQ improvement, loop versus no loop diuretics
    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
    Kansas City Cardiomyopathy Questionnaire clinical summary score improvement was greater in patients on loop diuretics compared to those not on loop diuretics (adjusted mean difference vs. placebo: +9.3 [6.5; 12.1] vs. +4.7 points [1.3, 8.2]; P = .042).
    1 context sentence
    Summary · context
    In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks
  4. 04HumanRandomized controlled trialSafety outcome

    Safety favoured semaglutide versus placebo across the diuretic subgroups.

    In plain wordsAcross diuretic subgroups, safety results favoured semaglutide over placebo.

    Peptide
    Semaglutide
    Outcome
    Not applicableSafety across diuretic subgroups
    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
    Safety also favoured semaglutide vs. placebo across the diuretic subgroups.
    1 context sentence
    Summary · context
    In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks
  5. 05HumanRandomized controlled trialEfficacy outcome

    In patients on loop diuretics, semaglutide improved the KCCQ clinical summary score by 9.3 points versus placebo.

    In plain wordsIn heart failure patients on loop diuretics, semaglutide improved symptom scores more than placebo.

    Peptide
    Semaglutide
    Outcome
    IncreaseKCCQ clinical summary score, loop diuretic users
    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).

    Measurements

    KCCQ-CSS adjusted mean difference vs placebo
    9.3 points
    loop diuretics

    Source sentences

    Summary
    Kansas City Cardiomyopathy Questionnaire clinical summary score improvement was greater in patients on loop diuretics compared to those not on loop diuretics (adjusted mean difference vs. placebo: +9.3 [6.5; 12.1] vs. +4.7 points [1.3, 8.2]; P = .042).
    1 context sentence
    Summary · context
    In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks
  6. 06HumanRandomized controlled trialEfficacy outcome

    In patients not on loop diuretics, semaglutide improved the KCCQ clinical summary score by 4.7 points versus placebo.

    In plain wordsIn heart failure patients not on loop diuretics, semaglutide improved symptom scores more than placebo.

    Peptide
    Semaglutide
    Outcome
    IncreaseKCCQ clinical summary score, patients not on loop diuretics
    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).

    Measurements

    KCCQ-CSS adjusted mean difference vs placebo
    4.7 points
    no loop diuretics

    Source sentences

    Summary
    Kansas City Cardiomyopathy Questionnaire clinical summary score improvement was greater in patients on loop diuretics compared to those not on loop diuretics (adjusted mean difference vs. placebo: +9.3 [6.5; 12.1] vs. +4.7 points [1.3, 8.2]; P = .042).
    1 context sentence
    Summary · context
    In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks
  7. 07HumanRandomized controlled trialEfficacy outcome

    From baseline to 52 weeks, loop diuretic dose decreased by 17% with semaglutide versus a 2.4% increase with placebo (P < .0001).

    In plain wordsLoop diuretic doses fell with semaglutide but rose slightly with placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseLoop diuretic dose change
    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).

    Measurements

    Loop diuretic dose decrease
    17%
    semaglutide
    Loop diuretic dose increase
    2.4%
    placebo

    Source sentences

    Summary
    From baseline to 52 weeks, loop diuretic dose decreased by 17% in the semaglutide group vs. a 2.4% increase in the placebo group (P < .0001).
    1 context sentence
    Summary · context
    In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks
  8. 08HumanRandomized controlled trialEfficacy outcome

    Semaglutide was more likely than placebo to result in loop diuretic dose reduction (OR 2.67).

    In plain wordsPeople on semaglutide were more likely than people on placebo to need a lower loop diuretic dose.

    Peptide
    Semaglutide
    Outcome
    IncreaseLoop diuretic dose reduction
    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).

    Measurements

    Odds ratio, dose reduction
    2.67
    semaglutide vs placebo

    Source sentences

    Summary
    Semaglutide (vs. placebo) was more likely to result in loop diuretic dose reduction (odds ratio [OR] 2.67 [95% CI 1.70, 4.18]) and less likely dose increase (OR 0.35 [95% CI 0.23, 0.53]; P < .001 for both) from baseline to 52 weeks.
    1 context sentence
    Summary · context
    In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks
  9. 09HumanRandomized controlled trialEfficacy outcome

    Semaglutide was less likely than placebo to result in loop diuretic dose increase (OR 0.35).

    In plain wordsPeople on semaglutide were less likely than people on placebo to need a higher loop diuretic dose.

    Peptide
    Semaglutide
    Outcome
    DecreaseLoop diuretic dose increase
    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).

    Measurements

    Odds ratio, dose increase
    0.35
    semaglutide vs placebo

    Source sentences

    Summary
    Semaglutide (vs. placebo) was more likely to result in loop diuretic dose reduction (odds ratio [OR] 2.67 [95% CI 1.70, 4.18]) and less likely dose increase (OR 0.35 [95% CI 0.23, 0.53]; P < .001 for both) from baseline to 52 weeks.
    1 context sentence
    Summary · context
    In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 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 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 pageClinicalTrials.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 pageClinicalTrials.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.

  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.

PepBank is a research reference. Talk to a doctor before you use any peptide.