Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes
- Design
- Randomized trial · 13165 participants · Hard outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationLong-standing type 2 diabetes with atherosclerotic disease; mean age 64.
- Could weight loss explain it?
- Specifically testedIndirectly informative on weight mediation: tirzepatide produces substantially more weight loss than dulaglutide yet was not superior for MACE, arguing against a simple dose-response between weight loss and cardiovascular events.
- Study tier
- Study tier 1Large double-blind active-comparator outcome trial.
- 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 13,165 people with type 2 diabetes and heart disease, tirzepatide was as good as, but not clearly better than, dulaglutide at preventing cardiovascular events over the trial, despite producing far more weight loss. Weight loss magnitude did not translate into extra cardiovascular protection here.
01Findings
What the study reported
- Drugs
- Tirzepatide, Dulaglutide
- Dose
- tirzepatide up to 15 mg vs dulaglutide 1.5 mg weekly
- Route
- subcutaneous
- Comparator
- dulaglutide (active comparator)
- Primary outcome
- CV death, MI or stroke (noninferiority margin 1.05)
- Effect
- HR 0.92 (12.2% vs 13.1%); noninferior; superiority not met
- 95% confidence interval
- 0.83 to 1.01 (95.3%)
- P value
- 0.003 noninferiority; 0.09 superiority
- Follow-up
- 8.8 years
- Adverse events
- More GI adverse events with tirzepatide.
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Mean age
- 64.1
- Sex distribution
- 29.0% female
- Bmi mean
- 32.6
- Diabetes status
- type 2 diabetes required (mean duration 14.7 years)
- Cvd status
- established ASCVD
- Sample size
- 13299
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 13299
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- active (dulaglutide)
- Follow up duration
- 8.8 years
- Outcome type
- hard
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- 1663 events
- Risk of bias
- not assessed (auto)
- Funding conflicts
- yes
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Eli Lilly
- Industry funded
- Yes
- Manufacturer
- Eli Lilly
- Sponsor role
- Sponsor designed and analysed.
- Author conflicts
- Authors report Eli Lilly relationships; sponsor co-authors.
- Independent replication
- unknown
- Notes
- Authors declare relationships with the drug's manufacturer: Eli Lilly, Eli Lilly
Funding is shown on every study and never used to score it.
03Claims
Claims this study bears on
- The cardiovascular benefit of GLP-1 receptor agonists is not explained by weight loss.Mixed
SURPASS-CVOT: tirzepatide (much greater weight loss) was noninferior but not superior to dulaglutide for MACE, arguing against a simple weight-loss dose-response for CV events.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Tirzepatide, a dual incretin agonist of the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors, has favorable effects on glycemic control and body weight. The effects on cardiovascular outcomes are uncertain. [METHODS] We conducted an active-comparator-controlled, double-blind, noninferiority trial in which patients with type 2 diabetes and atherosclerotic cardiovascular disease were randomly assigned in a 1:1 ratio to receive a weekly subcutaneous injection of tirzepatide (up to 15 mg) or dulaglutide (1.5 mg), an agent that has been shown to reduce the incidence of cardiovascular events. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke and was tested for noninferiority of tirzepatide to dulaglutide with a margin of 1.05 for the upper limit of the 95.3% confidence interval for the hazard ratio. An upper limit of less than 1.00 was considered to indicate superiority of tirzepatide to dulaglutide. [RESULTS] A total of 13,299 patients underwent randomization; 134 were subsequently excluded because they did not meet inclusion criteria. The modified intention-to-treat population thus included 6586 patients in the tirzepatide group and 6579 in the dulaglutide group. The mean (±SD) age of the patients was 64.1±8.8 years, 29.0% were women, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 32.6±5.5, the mean glycated hemoglobin level was 8.4±0.9%, and the mean duration of diabetes was 14.7±8.8 years. A primary end-point event occurred in 801 patients (12.2%) in the tirzepatide group and 862 (13.1%) in the dulaglutide group (hazard ratio, 0.92; 95.3% confidence interval, 0.83 to 1.01; P = 0.003 for noninferiority; P = 0.09 for superiority). The incidence of adverse events appeared to be similar in the two groups, although more gastrointestinal adverse events were observed in the tirzepatide group. [CONCLUSIONS] Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was noninferior to dulaglutide with respect to a composite of death from cardiovascular causes, myocardial infarction, or stroke. (Funded by Eli Lilly; SURPASS-CVOT ClinicalTrials.gov number, NCT04255433.).
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 41406444 first ingestion |