BACKGROUND: Tirzepatide, a dual incretin agonist of the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors, has favorable effects on glycemic control and body weight. The effects on cardiovascular outcomes are uncertain.
METHODS: We conducted an active-comparator-controlled, double-blind, noninferiority trial in which patients with type 2 diabetes and atherosclerotic cardiovascular disease were randomly assigned in a 1:1 ratio to receive a weekly subcutaneous injection of tirzepatide (up to 15 mg) or dulaglutide (1.5 mg), an agent that has been shown to reduce the incidence of cardiovascular events. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke and was tested for noninferiority of tirzepatide to dulaglutide with a margin of 1.05 for the upper limit of the 95.3% confidence interval for the hazard ratio. An upper limit of less than 1.00 was considered to indicate superiority of tirzepatide to dulaglutide.
RESULTS: A total of 13,299 patients underwent randomization; 134 were subsequently excluded because they did not meet inclusion criteria. The modified intention-to-treat population thus included 6586 patients in the tirzepatide group and 6579 in the dulaglutide group. The mean (±SD) age of the patients was 64.1±8.8 years, 29.0% were women, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 32.6±5.5, the mean glycated hemoglobin level was 8.4±0.9%, and the mean duration of diabetes was 14.7±8.8 years. A primary end-point event occurred in 801 patients (12.2%) in the tirzepatide group and 862 (13.1%) in the dulaglutide group (hazard ratio, 0.92; 95.3% confidence interval, 0.83 to 1.01; P = 0.003 for noninferiority; P = 0.09 for superiority). The incidence of adverse events appeared to be similar in the two groups, although more gastrointestinal adverse events were observed in the tirzepatide group.
CONCLUSIONS: Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was noninferior to dulaglutide with respect to a composite of death from cardiovascular causes, myocardial infarction, or stroke. (Funded by Eli Lilly; SURPASS-CVOT ClinicalTrials.gov number, NCT04255433.).
| Discipline Area | Score |
|---|---|
| Internal Medicine |  |
| Family Medicine (FM)/General Practice (GP) | |
| General Internal Medicine-Primary Care(US) | |
| Endocrine | |
| Cardiology | |
Not surprising that tirzepatide was non-inferior to a GLP-1 RA in reducing CV outcomes.
Seems to support what is already suspected.
Are the dual incretin agonists not better than GLP-1 RAs for clinical events and, if not, why not?
With the rising tide of tirzepatide use, it is great to see a trial providing safety information to give reassurance about its use in a high-risk ASCVD population. It would have been nice to see more women represented in the study and to have a better sense of whether there was a difference between those at the 15 mg dosage and those at lower dosages given the tolerability issues of high-dose tirzepatide. It was not unexpected to see more weight loss and better glycemic indices and other markers, and also disheartening to see that there was no difference in CVD outcomes with this better control. Overall, this provides me with reassurance to continue the increased prescribing pattern of tirzepatide.
