Effects of oral semaglutide on cardiovascular outcomes: A systematic review and meta-analysis.

Rebelo TG, de Araujo Paysano MLB, Matheus GTFU, Ribeiro DM, Said TB, Kelly FA

International journal of cardiology31 Jul 2025Cited by 7 (Europe PMC)

PMID40752805DOI10.1016/j.ijcard.2025.133683PepBankPUB-40752805

Publisher page PubMedAsk about this study

Summary

BackgroundCardiovascular disease remains a leading cause of morbidity and mortality in type 2 diabetic mellitus (T2DM) patients. While injectable GLP-1 RAs have demonstrated efficacy in reducing cardiovascular risk, an oral formulation of semaglutide was developed to improve accessibility and treatment adherence, however, its therapeutic potential has yet to be fully elucidated. This meta-analysis evaluates the efficacy of oral semaglutide on cardiovascular outcomes to better inform clinical decision-making.MethodsA systematic search was conducted in major databases for randomized controlled trials (RCTs) up to May 2025, with a primary outcome of cardiovascular events, expanded outcomes included nonfatal stroke, death from cardiovascular cause, and nonfatal myocardial infarction, and the secondary outcome was all-cause mortality. Statistical analysis was performed using RStudio, with heterogeneity assessed via I² statistics.ResultsA total of 13,875 patients were included, of whom 6935 received oral semaglutide and 6940 received placebo from the 5 eligible studies. A significant difference was observed for cardiovascular events with a risk ratio (RR) of 0.86 (95 % CI: 0.78-0.95; p = 0.0029; I² = 0 %) and hazard ratio (HR) of 0.85 (95 % CI: 0.77-0.95), respectively. In contrast, no significant difference was found for nonfatal stroke, all-cause mortality, death from cardiovascular causes, and nonfatal myocardial infarction.ConclusionThe meta-analysis revealed that oral semaglutide was cardioprotective in T2DM patients with consistent reductions in cardiovascular event risk. However, the lack of significance in the remaining outcomes underscores the need for further investigation.

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.

01HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes, oral semaglutide reduced cardiovascular events versus placebo in a meta-analysis of randomised trials.
In plain wordsIn adults with type 2 diabetes, oral semaglutide lowered the risk of cardiovascular events compared with placebo in pooled trials.
Peptide
Semaglutide
Outcome
DecreaseCardiovascular events
Study
n = 13,875
Comparator
Placebo
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · oralAs given in this study (human).
Measurements
Risk ratio
0.86
cardiovascular events
Hazard ratio
0.85
cardiovascular events
Source sentences
Summary
A significant difference was observed for cardiovascular events with a risk ratio (RR) of 0.86 (95 % CI: 0.78-0.95; p = 0.0029; I² = 0 %) and hazard ratio (HR) of 0.85 (95 % CI: 0.77-0.95), respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of 13,875 patients were included, of whom 6935 received oral semaglutide and 6940 received placebo from the 5 eligible studies.
Show in the study text Report a problemFND-4075280501
02HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes, oral semaglutide did not significantly change all-cause mortality versus placebo.
In plain wordsIn adults with type 2 diabetes, oral semaglutide did not change death from any cause compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeAll-cause mortality
Study
n = 13,875
Comparator
Placebo
Analysis
Secondary
Outcome group
Mortality · Whole body
Studied dose
Dose not stated · oralAs given in this study (human).
Source sentences
Summary
In contrast, no significant difference was found for nonfatal stroke, all-cause mortality, death from cardiovascular causes, and nonfatal myocardial infarction.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of 13,875 patients were included, of whom 6935 received oral semaglutide and 6940 received placebo from the 5 eligible studies.
Show in the study text Report a problemFND-4075280503
03HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes, oral semaglutide did not significantly change nonfatal stroke versus placebo.
In plain wordsIn adults with type 2 diabetes, oral semaglutide did not change the rate of nonfatal stroke compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeNonfatal stroke
Study
n = 13,875
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · oralAs given in this study (human).
Source sentences
Summary
In contrast, no significant difference was found for nonfatal stroke, all-cause mortality, death from cardiovascular causes, and nonfatal myocardial infarction.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of 13,875 patients were included, of whom 6935 received oral semaglutide and 6940 received placebo from the 5 eligible studies.
Show in the study text Report a problemFND-4075280502
04HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes, oral semaglutide did not significantly change death from cardiovascular causes versus placebo.
In plain wordsIn adults with type 2 diabetes, oral semaglutide did not change deaths from heart and vessel causes compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeDeath from cardiovascular causes
Study
n = 13,875
Comparator
Placebo
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated · oralAs given in this study (human).
Source sentences
Summary
In contrast, no significant difference was found for nonfatal stroke, all-cause mortality, death from cardiovascular causes, and nonfatal myocardial infarction.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of 13,875 patients were included, of whom 6935 received oral semaglutide and 6940 received placebo from the 5 eligible studies.
Show in the study text Report a problemFND-4075280504
05HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes, oral semaglutide did not significantly change nonfatal myocardial infarction versus placebo.
In plain wordsIn adults with type 2 diabetes, oral semaglutide did not change the rate of nonfatal heart attack compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeNonfatal myocardial infarction
Study
n = 13,875
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · oralAs given in this study (human).
Source sentences
Summary
In contrast, no significant difference was found for nonfatal stroke, all-cause mortality, death from cardiovascular causes, and nonfatal myocardial infarction.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of 13,875 patients were included, of whom 6935 received oral semaglutide and 6940 received placebo from the 5 eligible studies.
Show in the study text Report a problemFND-4075280505

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

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.

Version 2Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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