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Study · Randomized controlled trial · n = 2,229 · 2026

7 results

Oral Semaglutide and Heart Failure Outcomes in Persons With Type 2 Diabetes: A Secondary Analysis of the SOUL Randomized Clinical Trial.

Pop-Busui R, Rasmussen S, Deanfield JE, Buse JB, Marx N, Mulvagh SL, Inzucchi SE, Mann JFE, Emerson SS, Poulter NR, Engelmann MDM, Hovingh GK and 11 more

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Bayer Tanggaard K, Birkenfeld AL, Connelly KA, Haluzik M, Cavender MA, Kellerer M, Jhund PS, Gregersen S, Nielsen OW, Lam CSP, McGuire DK

JAMA internal medicine1 Apr 2026Cited by 8 (Europe PMC)

PMID41627802 (opens in a new tab)PMCIDPMC12865694 (opens in a new tab)DOI10.1001/jamainternmed.2025.7774 (opens in a new tab)PepBankPUB-41627802
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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 study7

7 results from studies that gave the peptide. 7 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes and heart failure at baseline, oral semaglutide lowered the risk of the composite HF outcome versus placebo (HR 0.78).

    In plain wordsIn adults with type 2 diabetes and heart failure, oral semaglutide lowered the risk of heart failure events more than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseComposite HF outcome in participants with HF at baseline
    Study

    n = 2,229

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated · oral · mean follow-up 47.5 monthsAs given in this study (human).

    Measurements

    HR
    0.78 ratio
    HF at baseline
    95% CI
    0.63 to 0.96 ratio
    HF at baseline

    Source sentences

    Summary
    For participants with HF at baseline, the hazard ratio (HR) for risk of the composite HF outcome with oral semaglutide vs placebo was 0.78 (95% CI, 0.63-0.96)
    2 context sentences
    Summary · context
    Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclerotic CV disease and/or chronic kidney disease, stratified according to the presence or absence of HF history at baseline.
    Summary · context
    Once-daily oral semaglutide or placebo in addition to standard of care.
  2. 02HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes and a history of heart failure, the MACE risk with oral semaglutide versus placebo was not significantly different (HR 0.83).

    In plain wordsIn adults with type 2 diabetes and a history of heart failure, oral semaglutide did not clearly change major heart events compared with placebo.

    Peptide
    Semaglutide
    Outcome
    No significant changeMACE in participants with HF history
    Study

    n = 2,229

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated · oral · mean follow-up 47.5 monthsAs given in this study (human).

    Measurements

    HR
    0.83 ratio
    HF history
    95% CI
    0.68 to 1.01 ratio
    HF history

    Source sentences

    Summary
    There was no heterogeneity in the risk reduction of MACE with oral semaglutide in participants with HF history (HR, 0.83; 95% CI, 0.68-1.01) or without HF history (HR, 0.86; 95% CI, 0.75-0.98) (P for interaction = .77).
    2 context sentences
    Summary · context
    Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclerotic CV disease and/or chronic kidney disease, stratified according to the presence or absence of HF history at baseline.
    Summary · context
    Once-daily oral semaglutide or placebo in addition to standard of care.
  3. 03HumanRandomized controlled trialSafety outcome

    In adults with type 2 diabetes and heart failure, serious adverse event occurrence was similar with oral semaglutide (53.8%) and placebo (57.1%).

    In plain wordsIn adults with type 2 diabetes and heart failure, serious side effects were about as common with oral semaglutide as with placebo.

    Peptide
    Semaglutide
    Outcome
    No significant changeSerious adverse events in participants with HF
    Study

    n = 2,229

    Comparator
    Placebo
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated · oral · mean follow-up 47.5 monthsAs given in this study (human).

    Measurements

    Serious adverse events
    53.8%
    oral semaglutide
    Serious adverse events
    57.1%
    placebo

    Source sentences

    Summary
    Serious adverse event occurrence among participants with HF was similar with oral semaglutide (594 [53.8%]) and placebo (642 [57.1%]).
    2 context sentences
    Summary · context
    Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclerotic CV disease and/or chronic kidney disease, stratified according to the presence or absence of HF history at baseline.
    Summary · context
    Once-daily oral semaglutide or placebo in addition to standard of care.
  4. 04HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes and heart failure with preserved ejection fraction, oral semaglutide lowered the risk of the composite HF outcome versus placebo (HR 0.59).

    In plain wordsIn adults with type 2 diabetes and heart failure with preserved ejection fraction, oral semaglutide lowered the risk of heart failure events more than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseComposite HF outcome with preserved ejection fraction
    Study

    n = 991

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated · oral · mean follow-up 47.5 monthsAs given in this study (human).

    Measurements

    HR
    0.59 ratio
    preserved ejection fraction
    95% CI
    0.39 to 0.86 ratio
    preserved ejection fraction

    Source sentences

    Summary
    the HR was 0.59 (95% CI, 0.39-0.86) in those with preserved ejection fraction
    2 context sentences
    Summary · context
    Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclerotic CV disease and/or chronic kidney disease, stratified according to the presence or absence of HF history at baseline.
    Summary · context
    Once-daily oral semaglutide or placebo in addition to standard of care.
  5. 05HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes and heart failure with reduced ejection fraction, oral semaglutide did not significantly change the risk of the composite HF outcome versus placebo (HR 0.98).

    In plain wordsIn adults with type 2 diabetes and heart failure with reduced ejection fraction, oral semaglutide did not change heart failure event risk compared with placebo.

    Peptide
    Semaglutide
    Outcome
    No significant changeComposite HF outcome with reduced ejection fraction
    Study

    n = 592

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated · oral · mean follow-up 47.5 monthsAs given in this study (human).

    Measurements

    HR
    0.98 ratio
    reduced ejection fraction
    95% CI
    0.7 to 1.38 ratio
    reduced ejection fraction

    Source sentences

    Summary
    0.98 (95% CI, 0.70-1.38) in those with reduced ejection fraction
    2 context sentences
    Summary · context
    Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclerotic CV disease and/or chronic kidney disease, stratified according to the presence or absence of HF history at baseline.
    Summary · context
    Once-daily oral semaglutide or placebo in addition to standard of care.
  6. 06HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes and no heart failure at baseline, oral semaglutide did not change the risk of the composite HF outcome versus placebo (HR 1.01).

    In plain wordsIn adults with type 2 diabetes and no heart failure, oral semaglutide did not change the risk of heart failure events compared with placebo.

    Peptide
    Semaglutide
    Outcome
    No significant changeComposite HF outcome in participants without HF at baseline
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated · oral · mean follow-up 47.5 monthsAs given in this study (human).

    Measurements

    HR
    1.01 ratio
    no HF at baseline
    95% CI
    0.84 to 1.2 ratio
    no HF at baseline

    Source sentences

    Summary
    the hazard ratio (HR) for risk of the composite HF outcome with oral semaglutide vs placebo was 0.78 (95% CI, 0.63-0.96) and was 1.01 (95% CI, 0.84-1.20) in those without HF at baseline
    2 context sentences
    Summary · context
    Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclerotic CV disease and/or chronic kidney disease, stratified according to the presence or absence of HF history at baseline.
    Summary · context
    Once-daily oral semaglutide or placebo in addition to standard of care.
  7. 07HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes and no history of heart failure, oral semaglutide reduced the MACE risk versus placebo (HR 0.86).

    In plain wordsIn adults with type 2 diabetes and no heart failure history, oral semaglutide lowered the risk of major heart events more than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseMACE in participants without HF history
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated · oral · mean follow-up 47.5 monthsAs given in this study (human).

    Measurements

    HR
    0.86 ratio
    no HF history
    95% CI
    0.75 to 0.98 ratio
    no HF history

    Source sentences

    Summary
    There was no heterogeneity in the risk reduction of MACE with oral semaglutide in participants with HF history (HR, 0.83; 95% CI, 0.68-1.01) or without HF history (HR, 0.86; 95% CI, 0.75-0.98) (P for interaction = .77).
    2 context sentences
    Summary · context
    Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclerotic CV disease and/or chronic kidney disease, stratified according to the presence or absence of HF history at baseline.
    Summary · context
    Once-daily oral semaglutide or placebo in addition to standard of care.

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 postedNCT03914326

A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes

Novo Nordisk A/Sn = 9,65117 Jun 2019 to 23 Aug 2024

Diabetes Mellitus, Type 2

Trial pageClinicalTrials.govUpdated 11 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.

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