Comparative Cardiovascular Outcomes of Tirzepatide and Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease

Tirzepatide was linked to a lower 1-year risk of major cardiovascular events than GLP-1 receptor agonists in patients with type 2 diabetes and atherosclerotic cardiovascular disease. In a retrospective study of over 16,000 matched patients, tirzepatide also showed lower risks of death, heart attack, and major limb events.

Observational study — retrospective propensity score-matched cohort study. Population: patients with type 2 diabetes and atherosclerotic cardiovascular disease. Sample size: 16,402 patients. Follow-up: 1 year. Interventions: tirzepatide.

Compared with GLP-1 receptor agonists, tirzepatide was associated with lower 1-year risks of major adverse cardiovascular events (HR, 0.75 [95% CI, 0.63-0.91]), all-cause mortality (HR, 0.69 [95% CI, 0.53-0.90]), major adverse limb events (HR, 0.59 [95% CI, 0.39-0.88]), and acute myocardial infarction (HR, 0.70 [95% CI, 0.53-0.93]). The authors state that results were robust across subgroups and sensitivity analyses. The primary outcome was a composite of major adverse cardiovascular events.

This paper offers real-world comparative data on tirzepatide versus GLP-1 receptor agonists for cardiovascular outcomes in a high-risk type 2 diabetes population. Researchers focusing on tirzepatide will find effect estimates for MACE, mortality, myocardial infarction, and limb events. The study does not establish causality and requires prospective validation.

Key findings

• Tirzepatide was associated with a lower risk of 1-year major adverse cardiovascular events (HR, 0.75 [95% CI, 0.63-0.91]) versus GLP-1 receptor agonists.
• All-cause mortality was lower with tirzepatide (HR, 0.69 [95% CI, 0.53-0.90]).
• Major adverse limb events were lower with tirzepatide (HR, 0.59 [95% CI, 0.39-0.88]).
• Acute myocardial infarction was lower with tirzepatide (HR, 0.70 [95% CI, 0.53-0.93]).

Limitations

• Observational retrospective design; associations do not prove causation.
• Propensity score matching cannot fully adjust for unmeasured confounders.
• Follow-up was limited to 1 year, so longer-term effects are unknown.

The record

• Journal: Journal of the American Heart Association 15(14): e047018
• Published: 2026-07-17
• PMID: 42466510 — DOI: 10.1161/jaha.125.047018
• MeSH terms: Humans, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Hypoglycemic Agents, Treatment Outcome, Retrospective Studies, Aged, Middle Aged, Female, Male, Atherosclerosis, Incretins, Propensity Score, Glucagon-Like Peptide-1 Receptor Agonists, Tirzepatide
• Author countries: Taiwan

Peptide profiles: Tirzepatide.

All indexed evidence: Tirzepatide trials & papers.

Related studies: Peripheral nerve complications from medications utilised for weight loss: a systematic…, Incretin-Based Therapies in Doxorubicin-Induced Cardiotoxicity: A Systematic Review of…, Effects of GLP-1 Receptor Agonists and Dual GIP/GLP-1 Receptor Agonists on Inflammatory…, Comparative effects of drugs for adults with overweight or obesity: systematic review….