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Lee, K.H

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Although the clinical relevance of the aforementioned cardiovascular risk factor alterations by tirzepatide will be assessed in the planned cardiovascular outcome study SURPASS-CVOT (NCT04255433), a pre-specified cardiovascular meta-analysis indicated that tirzepatide did not increase the risk of MACEs in participants with T2DM compared with controls.39 This pre-specified meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks included in the tirzepatide T2DM clinical development program, SURPASS.39 The pre-specified primary objective of this meta-analysis was the comparison of the time to the first occurrence of confirmed 4-component MACEs (MACE-4) (i.e., cardiovascular death, myocardial infarction, stroke, and hospitalization for unstable angina) between the pooled tirzepatide and control groups.39 The hazard ratios comparing tirzepatide versus controls were 0.80 (95% confidence interval [CI], 0.571.11) for MACE-4, 0.90 (95% CI, 0.501.61) for cardiovascular death, and 0.80 (95% CI, 0.511.25) for all-cause death.39 The effect of tirzepatide treatment on cardiovascular events has been studied in SURPASS-4, a trial involving patients with known coronary, peripheral arterial, or cerebrovascular diseases or those who were at a high risk of these diseases.5 In this study, no tirzepatide dose numerically increased the risk of cardiovascular events.5 Instead, for patients treated with the highest dose of tirzepatide (15 mg per week), the risk of developing any MACE (e.g., myocardial infarction, stroke, hospitalization for angina, or all-cause death) was estimated to be 0.50 (95% CI, 0.260.95).5 However, this was based on only 11 events in the tirzepatide 15 mg per week group (and 62 events with insulin glargine treatment).5 Collectively, tirzepatide did not increase the risk of MACEs in participants with T2DM compared with controls

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