Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes
- Design
- Randomized trial · 9650 participants · Hard outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationType 2 diabetes with established vascular or kidney disease.
- Could weight loss explain it?
- Possibly[Auto] Participants had obesity and/or type 2 diabetes and the abstract does not separate direct drug effects from weight loss or glycaemic improvement.
- Study tier
- Study tier 1[Auto] Large randomized trial with clinical outcomes (auto-provisional; risk of bias and consistency not yet assessed).
- Assessment
- Version 2 · curated · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
Oral semaglutide reduced major cardiovascular events by 14% over four years in 9,650 people with type 2 diabetes and vascular or kidney disease; kidney outcomes were not significantly improved. Same diabetes-population caveat as other outcome trials.
01Findings
What the study reported
- Drugs
- Semaglutide
- Dose
- oral, up to 14 mg daily
- Route
- oral
- Treatment duration
- mean 47.5 months
- Comparator
- placebo
- Primary outcome
- MACE (CV death, nonfatal MI, nonfatal stroke)
- Effect
- HR 0.86 (12.0% vs 13.8%); kidney composite not significantly different
- 95% confidence interval
- 0.77 to 0.96
- P value
- 0.006
- Follow-up
- mean 47.5 months
- Adverse events
- Serious adverse events 47.9% vs 50.3%; GI disorders 5.0% vs 4.4%.
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Age min
- 50
- Diabetes status
- type 2 diabetes required
- Cvd status
- ASCVD and/or CKD required
- Ckd status
- chronic kidney disease present in population (see abstract)
- Baseline condition
- chronic kidney disease
- Sample size
- 9650
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 9650
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo
- Follow up duration
- 50 years
- Outcome type
- hard
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% confidence interval, 0
- Risk of bias
- not assessed (auto)
- Funding conflicts
- yes
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Novo Nordisk
- Industry funded
- Yes
- Manufacturer
- Novo Nordisk
- Sponsor role
- Sponsor designed and analysed.
- Author conflicts
- Authors report Novo Nordisk relationships; sponsor co-authors.
- Independent replication
- unknown
- Notes
- Authors declare relationships with the drug's manufacturer: Novo Nordisk
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[BACKGROUND] The cardiovascular safety of oral semaglutide, a glucagon-like peptide 1 receptor agonist, has been established in persons with type 2 diabetes and high cardiovascular risk. An assessment of the cardiovascular efficacy of oral semaglutide in persons with type 2 diabetes and atherosclerotic cardiovascular disease, chronic kidney disease, or both is needed. [METHODS] In this double-blind, placebo-controlled, event-driven, superiority trial, we randomly assigned participants who were 50 years of age or older, had type 2 diabetes with a glycated hemoglobin level of 6.5 to 10.0%, and had known atherosclerotic cardiovascular disease, chronic kidney disease, or both to receive either once-daily oral semaglutide (maximal dose, 14 mg) or placebo, in addition to standard care. The primary outcome was major adverse cardiovascular events (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke), assessed in a time-to-first-event analysis. The confirmatory secondary outcomes included major kidney disease events (a five-point composite outcome). [RESULTS] Among the 9650 participants who had undergone randomization, the mean (±SD) follow-up was 47.5±10.9 months, and the median follow-up was 49.5 months. A primary-outcome event occurred in 579 of the 4825 participants (12.0%; incidence, 3.1 events per 100 person-years) in the oral semaglutide group, as compared with 668 of the 4825 participants (13.8%; incidence, 3.7 events per 100 person-years) in the placebo group (hazard ratio, 0.86; 95% confidence interval, 0.77 to 0.96; P = 0.006). The results for the confirmatory secondary outcomes did not differ significantly between the two groups. The incidence of serious adverse events was 47.9% in the oral semaglutide group and 50.3% in the placebo group; the incidence of gastrointestinal disorders was 5.0% and 4.4%, respectively. [CONCLUSIONS] Among persons with type 2 diabetes and atherosclerotic cardiovascular disease, chronic kidney disease, or both, the use of oral semaglutide was associated with a significantly lower risk of major adverse cardiovascular events than placebo, without an increase in the incidence of serious adverse events. (Funded by Novo Nordisk; SOUL ClinicalTrials.gov number, NCT03914326.).
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 40162642 first ingestion |