Last updated July 6, 2026
Key finding
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).
This study evaluated the effects of oral semaglutide on cardiovascular outcomes in patients with type 2 diabetes, finding a 14% reduction in major adverse cardiovascular events compared to placebo.
Quick read
The essential study design details in one scan.
EvidenceScore™
Moderate
Study type
RCTs
Follow-up
Long-Term (1–5 y)
Risk of bias
Some Concerns
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Plain-language summary
A plain-language read of the study’s main message and where it applies.
Study focus
This study evaluated the effects of oral semaglutide on cardiovascular outcomes in patients with type 2 diabetes, finding a 14% reduction in major adverse cardiovascular events compared to placebo.
These findings are clinically significant as they suggest that oral semaglutide not only helps manage blood sugar levels in type 2 diabetes but also may lower the risk of serious cardiovascular events. This dual benefit could lead to better overall health outcomes for patients with diabetes, a population at high risk for heart disease.
The study did not assess long-term cardiovascular outcomes beyond the trial duration. Findings may not be generalizable to all populations with type 2 diabetes. Subgroup analyses did not show significant interactions for several outcomes.
Published in
Publication details and source links for this paper.
Nikolaus M, John ED, Johannes FM, et al. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. Circulation. 2025;151(23):1639-1650. doi:10.1161/CIRCULATIONAHA.125.074545
Oral semaglutide reduced the risk of major adverse cardiovascular events by 14%.
Significant reduction in HbA1c levels was observed with oral semaglutide compared to placebo (p=0.05).
Body mass index decreased more with oral semaglutide than with placebo (p=0.05).
Evidence network
Understand where this research contributes within the broader evidence network.
This study contributes evidence to Semaglutide and Adverse events incidence, All-cause mortality, BMI, and 7 more.
This study contributes evidence to
Primary intervention
Semaglutide
Primary outcomes
Evidence topics
Primary intervention
Primary outcomes
Intervention and outcome relationships this study adds to the evidence network.
Editorial context
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Evidence network role
This section describes how the study fits into the current evidence network. It does not determine whether an intervention works on its own.
6
Related topics
10
Evidence pairs
997
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Evidence topic
Contributes evidence
Evidence topic
Contributes evidence
Evidence topic
Contributes evidence
Evidence topic
Contributes evidence
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Primary evidence
Evidence relationship
Related evidence
Evidence relationship
Save evidence
Evidence relationship
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Core evidence
The primary outcomes reported in this study.
Semaglutide → Adverse events incidence
Semaglutide → Adverse events incidence
Semaglutide → Estimated glomerular filtration rate
Semaglutide → Estimated glomerular filtration rate
Semaglutide → Time to cardiovascular death
Semaglutide → Time to cardiovascular death
Semaglutide → Time to first nonfatal myocardial infarction event
Semaglutide → Time to first nonfatal myocardial infarction event
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Explore related studies, evidence collections, and research questions.
Relationships organized using the Dediabetes Evidence Intelligence™ framework.
This study contributes to evidence on GLP-1 Receptor Agonists and HbA1c, GLP-1 Receptor Agonists and Cardiovascular Outcomes.
This study contributes to the evidence on the following intervention-outcome relationships.
Medications
Curated evidence collections and hubs this study is part of.
All studies on GLP-1 Receptor Agonists
Contributes to GLP-1 Receptor Agonists evidence base.
All studies measuring HbA1c
Measures HbA1c as a key outcome.
All studies measuring Cardiovascular Outcomes
Measures Cardiovascular Outcomes as a key outcome.
All studies measuring Adipokine and Angiogenic Markers
Measures Adipokine and Angiogenic Markers as a key outcome.
Latest published studies
Published within the last 2 years.
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11 results
6 results
11 results
11 results
6 results
Generated from the study's connected evidence using Evidence Intelligence™.
GLP-1 Receptor Agonists appears to improve HbA1c.
ConsistencyScore™: Results are consistent across studies.
Ranked evidence signals
HbA1c
EvidenceScore™ Strong | EvidenceScore™ 85.5 | strong positive | ConsistencyScore™ Consistent | 1 study
Why this answer: This answer is based on 32 supporting studies with consistent results and a positive effect signal.
Limitations
GLP-1 Receptor Agonists may improve Cardiovascular Outcomes.
ConsistencyScore™: Results are mixed and should be interpreted cautiously.
Ranked evidence signals
All-cause mortality
EvidenceScore™ Strong | EvidenceScore™ 82.9 | weak positive | ConsistencyScore™ Mixed | 1 study
Nonfatal stroke
EvidenceScore™ Strong | EvidenceScore™ 79.0 | weak negative | ConsistencyScore™ Mixed | 1 study
Why this answer: This answer is cautious because the available studies report mixed findings.
Limitations
GLP-1 Receptor Agonists may improve Body Mass Index.
ConsistencyScore™: Results are consistent across studies.
Ranked evidence signals
BMI
EvidenceScore™ Strong | EvidenceScore™ 79.0 | moderate positive | ConsistencyScore™ Consistent | 1 study
Why this answer: This answer is based on 15 supporting studies with consistent results and a positive effect signal.
Limitations
GLP-1 Receptor Agonists may improve Adipokine and Angiogenic Markers.
ConsistencyScore™: Results are consistent across studies.
Ranked evidence signals
LDL cholesterol
EvidenceScore™ Moderate | EvidenceScore™ 69.0 | moderate positive | ConsistencyScore™ Mixed | 1 study
Why this answer: This answer is based on 10 supporting studies with consistent results and a positive effect signal.
Limitations
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