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Study · Randomized controlled trial · n = 4,286 · 2024

10 results

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial.

Deanfield J, Verma S, Scirica BM, Kahn SE, Emerson SS, Ryan D, Lingvay I, Colhoun HM, Plutzky J, Kosiborod MN, Hovingh GK, Hardt-Lindberg S and 8 more

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Frenkel O, Weeke PE, Rasmussen S, Goudev A, Lang CC, Urina-Triana M, Pietilä M, Lincoff AM

Lancet (London, England)1 Aug 2024Cited by 221 (Europe PMC)

PMID39181597 (opens in a new tab)DOI10.1016/s0140-6736(24)01498-3 (opens in a new tab)PepBankPUB-39181597
Publisher pagePubMedAsk about this study
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Summary

BackgroundSemaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure.MethodsThe SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597.FindingsBetween Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype.InterpretationIn patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group.FundingNovo Nordisk.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

10 results from studies that gave the peptide. 10 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In adults with obesity, cardiovascular disease and heart failure at enrolment, semaglutide lowered the risk of major adverse cardiovascular events versus placebo.

    In plain wordsIn adults with obesity, heart disease and heart failure, semaglutide lowered the risk of major heart events more than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseMACE in patients with heart failure at enrolment
    Study

    n = 4,286

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    2·4 mg once weekly · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19).
    1 context sentence
    Summary · context
    Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo.
  2. 02HumanRandomized controlled trialEfficacy outcome

    In adults with obesity, cardiovascular disease and heart failure at enrolment, semaglutide lowered the risk of the composite heart failure endpoint versus placebo.

    In plain wordsIn adults with obesity, heart disease and heart failure, semaglutide lowered the risk of heart failure events or heart death more than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseHeart failure composite endpoint in patients with heart failure at enrolment
    Study

    n = 4,286

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    2·4 mg once weekly · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19).
    1 context sentence
    Summary · context
    Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo.
  3. 03HumanRandomized controlled trialEfficacy outcome

    In adults with obesity, cardiovascular disease and heart failure at enrolment, semaglutide lowered the risk of cardiovascular death versus placebo.

    In plain wordsIn adults with obesity, heart disease and heart failure, semaglutide lowered the risk of death from heart causes more than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseCardiovascular death in patients with heart failure at enrolment
    Study

    n = 4,286

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    2·4 mg once weekly · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19).
    1 context sentence
    Summary · context
    Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo.
  4. 04HumanRandomized controlled trialEfficacy outcome

    In adults with obesity, cardiovascular disease and heart failure at enrolment, semaglutide lowered the risk of all-cause death versus placebo; the confidence interval upper bound was at no difference.

    In plain wordsIn adults with obesity, heart disease and heart failure, semaglutide was linked to a lower risk of death from any cause than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseAll-cause death in patients with heart failure at enrolment
    Study

    n = 4,286

    Comparator
    Placebo
    Outcome group
    Mortality · Cardiovascular
    Studied dose
    2·4 mg once weekly · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19).
    1 context sentence
    Summary · context
    Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo.
  5. 05HumanRandomized controlled trialEfficacy outcome

    In adults with heart failure with preserved ejection fraction, semaglutide lowered the risk of major adverse cardiovascular events versus placebo.

    In plain wordsIn adults with heart failure with preserved pumping function, semaglutide lowered the risk of major heart events more than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseMACE in heart failure with preserved ejection fraction
    Study

    n = 2,273

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    2·4 mg once weekly · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE
    1 context sentence
    Summary · context
    Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo.
  6. 06HumanRandomized controlled trialEfficacy outcome

    In adults with heart failure with preserved ejection fraction, the composite heart failure endpoint was not clearly lower with semaglutide than with placebo; the confidence interval included 1.

    In plain wordsIn adults with heart failure with preserved pumping function, semaglutide showed no clear difference from placebo in heart failure events or heart death.

    Peptide
    Semaglutide
    Outcome
    No significant changeHeart failure composite in heart failure with preserved ejection fraction
    Study

    n = 2,273

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    2·4 mg once weekly · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint)
    1 context sentence
    Summary · context
    Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo.
  7. 07HumanRandomized controlled trialEfficacy outcome

    In adults with heart failure with reduced ejection fraction, semaglutide lowered the risk of major adverse cardiovascular events versus placebo.

    In plain wordsIn adults with heart failure with reduced pumping function, semaglutide lowered the risk of major heart events more than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseMACE in heart failure with reduced ejection fraction
    Study

    n = 1,347

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    2·4 mg once weekly · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE
    1 context sentence
    Summary · context
    Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo.
  8. 08HumanRandomized controlled trialEfficacy outcome

    In adults with heart failure with reduced ejection fraction, the composite heart failure endpoint was not clearly lower with semaglutide than with placebo; the confidence interval included 1.

    In plain wordsIn adults with heart failure with reduced pumping function, semaglutide showed no clear difference from placebo in heart failure events or heart death.

    Peptide
    Semaglutide
    Outcome
    No significant changeHeart failure composite in heart failure with reduced ejection fraction
    Study

    n = 1,347

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    2·4 mg once weekly · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint)
    1 context sentence
    Summary · context
    Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo.
  9. 09HumanRandomized controlled trialEfficacy outcome

    For MACE and the heart failure composite, the benefit of semaglutide did not differ significantly across baseline age, sex, BMI, NYHA status or diuretic use.

    In plain wordsThe heart benefit of semaglutide over placebo did not differ clearly by age, sex, BMI, heart failure class or diuretic use.

    Peptide
    Semaglutide
    Outcome
    No significant changeTreatment effect across baseline characteristics
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    2·4 mg once weekly · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use.
    1 context sentence
    Summary · context
    Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo.
  10. 10HumanRandomized controlled trialSafety outcome

    Serious adverse events were less frequent with semaglutide than with placebo, regardless of heart failure subtype.

    In plain wordsSerious side effects happened less often with semaglutide than with placebo, whatever the type of heart failure.

    Peptide
    Semaglutide
    Outcome
    DecreaseSerious adverse events
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Adverse events · Cardiovascular
    Studied dose
    2·4 mg once weekly · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype.
    1 context sentence
    Summary · context
    Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo.

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

CompletedPhase 3Results postedNCT03574597

Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity

Novo Nordisk A/Sn = 17,60424 Oct 2018 to 29 Jun 2023

Overweight · Obesity

Trial pageClinicalTrials.govUpdated 30 Aug 2024

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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