Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
- Design
- Randomized trial · 3297 participants · Hard outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationType 2 diabetes with high CV risk.
- Could weight loss explain it?
- PossiblyNot separated; retinopathy signal may relate to rapid glycaemic improvement.
- Study tier
- Study tier 2Moderate-sized noninferiority CVOT; superiority was a post hoc interpretation. Important source of the retinopathy safety signal.
- 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.
In 3,297 people with type 2 diabetes, semaglutide lowered cardiovascular events over two years but increased diabetic retinopathy complications. Context for the retinopathy safety topic; not applicable outside diabetes.
01Findings
What the study reported
- Drugs
- Semaglutide
- Dose
- 0.5 or 1.0 mg once weekly
- Route
- subcutaneous
- Treatment duration
- 104 weeks
- Comparator
- placebo
- Primary outcome
- CV death, nonfatal MI or nonfatal stroke (noninferiority)
- Effect
- HR 0.74 (6.6% vs 8.9%); stroke HR 0.61; retinopathy complications HR 1.76
- 95% confidence interval
- 0.58 to 0.95
- P value
- <0.001 noninferiority
- Follow-up
- 104 weeks
- Adverse events
- Retinopathy complications HR 1.76 (1.11-2.78); GI discontinuations higher.
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Diabetes status
- type 2 diabetes required
- Cvd status
- 83% with established CVD or CKD
- Ckd status
- chronic kidney disease present in population (see abstract)
- Baseline condition
- chronic kidney disease
- Sample size
- 3297
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 3297
- Randomization
- yes
- Blinding
- not stated
- Comparator
- placebo
- Follow up duration
- 104 weeks
- Outcome type
- hard
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- 254 events; noninferiority design
- Risk of bias
- low; superiority not prespecified
- 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
- class-level
- 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] Regulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown. [METHODS] We randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. We hypothesized that semaglutide would be noninferior to placebo for the primary outcome. The noninferiority margin was 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio. [RESULTS] At baseline, 2735 of the patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both. The primary outcome occurred in 108 of 1648 patients (6.6%) in the semaglutide group and in 146 of 1649 patients (8.9%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.58 to 0.95; P<0.001 for noninferiority). Nonfatal myocardial infarction occurred in 2.9% of the patients receiving semaglutide and in 3.9% of those receiving placebo (hazard ratio, 0.74; 95% CI, 0.51 to 1.08; P=0.12); nonfatal stroke occurred in 1.6% and 2.7%, respectively (hazard ratio, 0.61; 95% CI, 0.38 to 0.99; P=0.04). Rates of death from cardiovascular causes were similar in the two groups. Rates of new or worsening nephropathy were lower in the semaglutide group, but rates of retinopathy complications (vitreous hemorrhage, blindness, or conditions requiring treatment with an intravitreal agent or photocoagulation) were significantly higher (hazard ratio, 1.76; 95% CI, 1.11 to 2.78; P=0.02). Fewer serious adverse events occurred in the semaglutide group, although more patients discontinued treatment because of adverse events, mainly gastrointestinal. [CONCLUSIONS] In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide. (Funded by Novo Nordisk; SUSTAIN-6 ClinicalTrials.gov number, NCT01720446 .).
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 27633186 first ingestion |