medwireNews: A meta-analysis of individual patient data from the SURPASS clinical trial program suggests that tirzepatide has at least a neutral cardiovascular (CV) safety profile.
The prespecified analysis included prospectively recorded and centrally adjudicated major adverse CV events (MACE) from the phase 2 trial of tirzepatide, plus SURPASS-1, 2, 3, 4, and 5 and the Japan-specific trial SURPASS J-mono.
These provided data from 7215 trial participants, 142 of whom had at least one MACE-4 outcome (60 with myocardial infarction, 30 with stroke, 47 with CV death, and 14 with hospitalization for unstable angina). Most events occurred within SURPASS-4, which enrolled a high-risk population, with 86.9% of participants having established CV disease, compared with 5.4–18.3% of the other trial populations.
The trial follow-up times ranged from 30 to 56 weeks, the average tirzepatide dose was 9.9 mg/week, and the comparator treatments included both CV-neutral interventions (placebo, insulin glargine, insulin degludec) and those with proven CV benefits (dulaglutide, semaglutide).
The risk for MACE-4 outcomes was no higher or lower with tirzepatide than with the comparator treatments, with a hazard ratio of 0.80 and a 95% confidence interval (CI) of 0.57–1.11.
“Furthermore, the incidence of MACE-4 with tirzepatide starts to diverge from the control groups after approximately 1 year,” write Naveed Sattar (University of Glasgow, UK) and co-researchers in Nature Medicine.
The findings were similar for MACE-3 outcomes (without unstable angina), for MACE-3 plus hospitalization for heart failure, and for all-cause mortality.
And there were no differences in MACE-4 outcomes across subgroups defined by age, sex, race, country, baseline glycated hemoglobin, and baseline use of sodium-glucose cotransporter inhibitors.
“Collectively, these data meet the regulatory cardiovascular safety criterion for consideration of a novel anti-hyperglycemic medication for initial approval, statistically excluding the upper confidence limit of the 95% CI of 1.8,” say the study authors.
“Furthermore, some of these findings provide optimism for the potential positive cardiovascular effects of tirzepatide (aiming for a maximum dose of 15 mg per day) being tested in the ongoing outcome trial SURPASS-CVOT (NCT04255433).”
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