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

In 30 seconds

This systematic review and meta-analysis pooled randomized controlled trials of subcutaneous semaglutide or tirzepatide in adults with type 2 diabetes and/or obesity, assessing coronary artery disease (CAD)-related outcomes. Across 45 trials, semaglutide was associated with lower pooled estimates for several outcomes, including the broad CAD-related composite (RR = 0.80, 95% CI [0.73-0.87]; p < 0.001), acute coronary syndrome, myocardial infarction, unstable angina, and angina pectoris. Most pooled tirzepatide estimates were not statistically significant; evidence was less precise because CAD events were fewer and outcome data limited.

Key findings

• Semaglutide was associated with a lower broad CAD-related composite risk: RR = 0.80, 95% CI [0.73-0.87]; p < 0.001.
• Semaglutide pooled estimates were lower for acute coronary syndrome (RR = 0.77, 95% CI [0.70-0.85]; p < 0.001) and myocardial infarction (RR = 0.70, 95% CI [0.62-0.80]; p < 0.001).
• Tirzepatide’s broad CAD-related composite estimate was not statistically significant (RR = 0.74, 95% CI [0.52-1.07]; p = 0.110).
• A lower estimate for trial-reported CAD events with tirzepatide was based on fewer events and considered exploratory.

Why it matters

CAD outcomes are clinically important in adults with type 2 diabetes and/or obesity. This synthesis suggests that semaglutide trial data show lower pooled estimates across several CAD phenotypes, while the evidence for tirzepatide is less conclusive. The findings also highlight the value of dedicated cardiovascular outcome trials and consistent reporting of CAD events when assessing cardiovascular effects.

What to keep in mind

CAD-specific outcome data were limited, particularly for tirzepatide, and its CAD-event finding was based on fewer events. The authors call for longer follow-up and more standardized outcome reporting.