Coronary artery disease -related outcomes associated with semaglutide and tirzepatide in type 2 diabetes mellitus and obesity: a systematic review and meta-analysis

In a meta-analysis of 45 randomized trials, semaglutide was associated with lower risks of several coronary artery disease-related outcomes in adults with type 2 diabetes and/or obesity, whereas tirzepatide's pooled estimates were not statistically significant for most CAD outcomes.

Narrative review — Systematic review and meta-analysis of RCTs. Population: Adults with type 2 diabetes and/or obesity. Sample size: 45 included trials. Interventions: subcutaneous semaglutide; subcutaneous tirzepatide.

Among the 45 included trials, semaglutide showed lower pooled estimates for the broad CAD-related composite (RR = 0.80, 95% CI 0.73–0.87), acute coronary syndrome (RR = 0.77, 95% CI 0.70–0.85), myocardial infarction (RR = 0.70, 95% CI 0.62–0.80), unstable angina (RR = 0.82, 95% CI 0.70–0.96), and angina pectoris (RR = 0.73, 95% CI 0.60–0.89). For tirzepatide, pooled estimates were not statistically significant for most CAD-related outcomes, including the broad CAD-related composite (RR = 0.74, 95% CI 0.52–1.07; p = 0.110). A lower pooled estimate was observed for trial-reported CAD events in tirzepatide trials, but this was based on fewer events and interpreted as exploratory.

For researchers studying tirzepatide, this paper offers a pooled synthesis of CAD-related outcomes across randomized trials, showing that tirzepatide's estimates were generally not statistically significant and that CAD-specific data remain limited. It does not establish that tirzepatide reduces or increases coronary artery disease risk, and the authors call for dedicated cardiovascular outcome trials and longer follow-up.

Key findings

• Semaglutide was associated with a lower risk of the broad CAD-related composite (RR = 0.80, 95% CI 0.73–0.87).
• Semaglutide was associated with lower risk of acute coronary syndrome (RR = 0.77, 95% CI 0.70–0.85) and myocardial infarction (RR = 0.70, 95% CI 0.62–0.80).
• Semaglutide was associated with lower risk of unstable angina (RR = 0.82, 95% CI 0.70–0.96) and angina pectoris (RR = 0.73, 95% CI 0.60–0.89).
• Tirzepatide showed no statistically significant effect on the broad CAD-related composite (RR = 0.74, 95% CI 0.52–1.07; p = 0.110).
• A lower pooled estimate for trial-reported CAD events in tirzepatide trials was exploratory because of fewer events.

Limitations

• Evidence for tirzepatide was less precise because of fewer CAD-related events and limited CAD-specific outcome data.
• The trials used different control groups, limiting direct comparability.
• The authors noted that more standardized reporting of CAD-related outcomes is needed.
• As a meta-analysis, pooled estimates may be affected by differences in outcome definitions and trial designs across studies.

The record

• Journal: Nutrition, metabolism, and cardiovascular diseases : NMCD: 104859
• Published: 2026-07-07
• PMID: 42469143 — DOI: 10.1016/j.numecd.2026.104859
• Author countries: China

Peptide profiles: Tirzepatide.

All indexed evidence: Tirzepatide trials & papers.

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