Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
- Design
- Randomized trial · 9340 participants · Hard outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationType 2 diabetes at high CV risk; landmark trial establishing class CV benefit in diabetes.
- Could weight loss explain it?
- PossiblyNot addressed in the abstract: it reports no weight or HbA1c changes and no mediation analysis, so it does not separate direct drug effects from weight loss or glucose lowering.
- Study tier
- Study tier 1[Auto] Large randomized trial with clinical outcomes (auto-provisional; risk of bias and consistency not yet assessed).
- Assessment
- Version 5 · Checked against the source by AI · Oct 19, 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.
Landmark 2016 trial: in 9,340 people with type 2 diabetes at high cardiovascular risk, liraglutide reduced major cardiovascular events (HR 0.87), cardiovascular death and death from any cause over a median 3.8 years. On their own, nonfatal heart attack, nonfatal stroke and hospital admission for heart failure were not significantly reduced. Context for later trials; not applicable to people without diabetes.
01Findings
What the study reported
- Drugs
- Liraglutide
- Dose
- 1.8 mg daily
- Route
- subcutaneous
- Treatment duration
- median 3.8 years
- Comparator
- placebo
- Primary outcome
- CV death, nonfatal MI or nonfatal stroke
- Effect
- HR 0.87 (13.0% vs 14.9%); CV death HR 0.78; all-cause death HR 0.85
- 95% confidence interval
- 0.78 to 0.97
- P value
- 0.01 for superiority
- Follow-up
- median 3.8 years
- Adverse events
- GI events most common cause of discontinuation; pancreatitis not increased.
- Limitations
- Not extracted
Who was studied
- Obesity status
- not required (mean BMI ~32.5, full text, not checked)
- Diabetes status
- type 2 diabetes required (all)
- Cvd status
- high CV risk or established CVD required
- Sample size
- 9340
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 9340
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo
- Follow up duration
- median 3.8 years
- Outcome type
- hard
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 0.78 to 0.97
- Risk of bias
- not assessed (auto)
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Novo Nordisk and NIH
- Industry funded
- Partial
- Manufacturer
- Novo Nordisk
- Sponsor role
- Sponsor designed and analysed with steering committee.
- Author conflicts
- Authors report Novo Nordisk relationships; sponsor co-authors.
- Independent replication
- class-level consistency (SUSTAIN-6, REWIND)
- 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 effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. [METHODS] In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. [RESULTS] A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. [CONCLUSIONS] In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048.).
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 27295427 first ingestion |