Efficacy and Safety of Tirzepatide Versus Dulaglutide in Type 2 Diabetes With or Without Established Atherosclerotic Cardiovascular Disease: A Network Meta-Analysis of Randomized Clinical Trials
- Design
- Meta-analysis · 14348 participants · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Different population[Auto] Synthesis of studies conducted predominantly in people with type 2 diabetes.
- 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 2[Auto] Systematic review/meta-analysis of randomized trials (auto-provisional; heterogeneity and included-study quality not assessed).
- Assessment
- Version 1 · automatic, not yet reviewed by a person · 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.
[Auto, unreviewed; quoted from abstract conclusions] Higher TZP doses potentially improve efficacy, while lower TZP/DULA doses enhance tolerability, supporting individualized T2DM care. However, these findings should be interpreted cautiously because several comparisons are indirect, many participants had not reached their maintenance dose, several safety outcomes were based on limited event counts, and significant inconsistency was observed for early body-weight outcomes.
01Findings
What the study reported
- Drugs
- Dulaglutide, Tirzepatide
- Dose
- 15 mg
- Comparator
- Dulaglutide
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- 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 present (all or most)
- Cvd status
- cardiovascular disease present in population (see abstract)
- Sample size
- 14348
Study quality details
- Study design
- Meta-analysis
- Sample size
- 14348
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- active comparator
- Follow up duration
- not stated
- Outcome type
- mixed
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% CI -4
- Risk of bias
- not assessed (auto)
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- Eli Lilly, Lilly, AstraZeneca, Amgen, Pfizer
- Sponsor role
- not reported in abstract
- Author conflicts
- Dr. Fonarow has consulted for Abbott, Amgen, AstraZeneca, Bayer, Boehinger Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. The remaining authors declare no conflicts of interest.
- 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.
04Source
The source, as retrieved
Abstract
[BACKGROUND AND AIM] This network meta-analysis addresses the limited dose-specific comparative evidence by evaluating different doses of tirzepatide (TZP) versus dulaglutide (DULA) for glycemic control, weight loss, and safety in type 2 diabetes mellitus (T2DM). [METHODS] Following PRISMA and Cochrane guidance, we searched major databases for RCTs comparing TZP and DULA in adults with T2DM. Efficacy outcomes included body weight change (Weeks 12 and 16) and mean HbA1c change (Weeks 12 and 24). Safety outcomes included mortality, cardiovascular events, and adverse events (AEs). SUCRA ranking was used and analysis performed in RStudio (v4.5.1). [RESULTS] Four RCTs comprising 14,348 participants contributed to a seven-node network. However, Nicholls et al. 2025 had the majority of sample size (n = 13,165). TZP 15 mg achieved the greatest reduction in body weight at Week 16 (mean difference [MD] vs. TZP 5 mg: -2.68 kg; 95% CI -4.98 to -0.38), while TZP 1 mg (MD: 4.39 kg; 95% CI 1.28 to 7.51) and DULA 0.75 mg (MD: 3.10 kg; 95% CI 0.25 to 5.96) were associated with smaller reductions relative to TZP 5 mg. TZP 15 mg also produced the largest HbA1c reduction at Week 24 (MD vs. TZP 5 mg: -0.40%; 95% CI -0.62 to -0.19), compared with TZP 10 mg (MD: -0.23%; 95% CI -0.44 to -0.02) and DULA 1.5 mg (MD: 0.67%; 95% CI 0.25 to 1.09). No significant differences were observed between treatments for all-cause mortality or major cardiovascular events. Gastrointestinal AEs were more frequent with higher TZP doses, especially TZP 15 mg vs. TZP 5 mg for nausea, while serious AEs and severe hypoglycemia were similar across doses. [CONCLUSION] Higher TZP doses potentially improve efficacy, while lower TZP/DULA doses enhance tolerability, supporting individualized T2DM care. However, these findings should be interpreted cautiously because several comparisons are indirect, many participants had not reached their maintenance dose, several safety outcomes were based on limited event counts, and significant inconsistency was observed for early body-weight outcomes.