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Study · Randomized controlled trial · n = 9,650 · 2025

6 results

Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial.

Marx N, Deanfield JE, Mann JFE, Arechavaleta R, Bain SC, Bajaj HS, Bayer Tanggaard K, Birkenfeld AL, Buse JB, Davicevic-Elez Z, Desouza C, Emerson SS and 10 more

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Engelmann MDM, Hovingh GK, Inzucchi SE, Jhund PS, Mulvagh SL, Pop-Busui R, Poulter NR, Rasmussen S, Tu ST, McGuire DK

Circulation29 Mar 2025Cited by 49 (Europe PMC)

PMID40156843 (opens in a new tab)PMCIDPMC12144549 (opens in a new tab)DOI10.1161/circulationaha.125.074545 (opens in a new tab)PepBankPUB-40156843
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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 study6

6 results from studies that gave the peptide. 6 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes and cardiovascular or chronic kidney disease, oral semaglutide lowered the risk of the primary cardiovascular outcome by 14% versus placebo.

    In plain wordsIn adults with type 2 diabetes and heart or kidney disease, oral semaglutide lowered the risk of major cardiovascular events by 14% compared with placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseTime to first major adverse cardiovascular event, overall population
    Study

    n = 9,650

    Comparator
    Placebo
    Analysis
    Primary
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated · oralAs given in this study (human).

    Measurements

    Hazard ratio
    0.86 ratio
    oral semaglutide vs placebo, overall

    Source sentences

    Summary
    Over a mean follow-up of 47.5±10.9 months, the risk of the primary outcome in the overall trial population was 14% lower for oral semaglutide versus placebo (hazard ratio, 0.86; 95% CI, 0.77-0.96).
    2 context sentences
    Summary · context
    The primary outcome was time to first major adverse cardiovascular event, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
    Summary · context
    The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease to oral semaglutide or placebo.
  2. 02HumanRandomized controlled trialEfficacy outcome

    The effect of oral semaglutide on major cardiovascular events did not differ by baseline SGLT2i use (P-interaction 0.66).

    In plain wordsOral semaglutide worked about the same on major cardiovascular events whether or not people took an SGLT2 inhibitor at baseline, compared with placebo.

    Peptide
    Semaglutide
    Outcome
    No significant changeHeterogeneity of effect by baseline SGLT2i use (P-interaction)
    Study

    n = 9,650

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated · oralAs given in this study (human).

    Measurements

    P-interaction
    0.66
    baseline SGLT2i use

    Source sentences

    Summary
    P-interaction, 0.66).
    1 context sentence
    Summary · context
    The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease to oral semaglutide or placebo.
  3. 03HumanRandomized controlled trialEfficacy outcome

    There was no evidence that the effect of oral semaglutide on major cardiovascular events differed by any in-trial SGLT2i use versus no use.

    In plain wordsOral semaglutide worked about the same on major cardiovascular events whether or not people used an SGLT2 inhibitor during the trial.

    Peptide
    Semaglutide
    Outcome
    No significant changeMajor adverse cardiovascular events by any in-trial SGLT2i use
    Study

    n = 9,650

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated · oralAs given in this study (human).

    Source sentences

    Summary
    An analysis of major adverse cardiovascular events by any in-trial SGLT2i use versus no use also showed no evidence of heterogeneity in the effects of oral semaglutide.
    2 context sentences
    Summary · context
    As prespecified, participants were analyzed according to baseline use of SGLT2i (yes, n=2596; no, n=7054), and subsequently for any use of SGLT2i during the trial (yes, n=4718; no, n=4932).
    Summary · context
    The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease to oral semaglutide or placebo.
  4. 04HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes who did not take an SGLT2 inhibitor at baseline, oral semaglutide lowered major cardiovascular events versus placebo (hazard ratio 0.84).

    In plain wordsIn adults with type 2 diabetes not taking an SGLT2 inhibitor, oral semaglutide lowered the risk of major cardiovascular events compared with placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseMajor adverse cardiovascular events in participants not taking SGLT2i at baseline
    Study

    n = 7,054

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated · oralAs given in this study (human).

    Measurements

    Hazard ratio
    0.84 ratio
    baseline non-users of SGLT2i

    Source sentences

    Summary
    436 of 3529 versus 510 of 3525, respectively, in participants not taking SGLT2i at baseline (hazard ratio, 0.84; 95% CI, 0.74-0.95
    2 context sentences
    Summary · context
    As prespecified, participants were analyzed according to baseline use of SGLT2i (yes, n=2596; no, n=7054), and subsequently for any use of SGLT2i during the trial (yes, n=4718; no, n=4932).
    Summary · context
    The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease to oral semaglutide or placebo.
  5. 05HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes who took an SGLT2 inhibitor at baseline, the hazard ratio for major cardiovascular events with oral semaglutide versus placebo was 0.89, with a confidence interval that included 1.

    In plain wordsIn adults with type 2 diabetes already taking an SGLT2 inhibitor, oral semaglutide showed no clear difference from placebo in major cardiovascular events.

    Peptide
    Semaglutide
    Outcome
    No significant changeMajor adverse cardiovascular events in participants taking SGLT2i at baseline
    Study

    n = 2,596

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated · oralAs given in this study (human).

    Measurements

    Hazard ratio
    0.89 ratio
    baseline SGLT2i users

    Source sentences

    Summary
    In those taking SGLT2i at baseline, there were 143 of 1296 (semaglutide) versus 158 of 1300 (placebo) primary outcome events (hazard ratio, 0.89; 95% CI, 0.71-1.11
    2 context sentences
    Summary · context
    As prespecified, participants were analyzed according to baseline use of SGLT2i (yes, n=2596; no, n=7054), and subsequently for any use of SGLT2i during the trial (yes, n=4718; no, n=4932).
    Summary · context
    The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease to oral semaglutide or placebo.
  6. 06HumanRandomized controlled trialSafety outcome

    Adverse event profiles of oral semaglutide were similar with or without concomitant SGLT2i.

    In plain wordsSide effects of oral semaglutide were similar whether or not people also took an SGLT2 inhibitor.

    Peptide
    Semaglutide
    Outcome
    No significant changeAdverse event profile with or without concomitant SGLT2i
    Study

    n: not reported in source

    Comparator
    Oral semaglutide without concomitant SGLT2i
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated · oralAs given in this study (human).

    Source sentences

    Summary
    The adverse event profiles of oral semaglutide with or without concomitant SGLT2i were similar.
    2 context sentences
    Summary · context
    Safety was evaluated by comparing the incidence of serious adverse events.
    Summary · context
    The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease to oral semaglutide 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 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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