Weekly Journal Scan: Tirzepatide did not SURPASS the cardiovascular benefits of dulaglutide in type 2 diabetes

This comment refers to ‘Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes’ which was published in the New England Journal of Medicine, https://doi.org/10.1056/NEJMoa2505928. Over the past decade, incretin-based therapies have reshaped cardiovascular risk management in type 2 diabetes. Large cardiovascular outcome trials have consistently demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major adverse cardiovascular events, largely driven by effects on ASCVD outcomes rather than HF.2–5 Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, showed unprecedented efficacy on glycaemic control and body weight, raising expectations that these metabolic advantages - might translate into incremental cardiovascular benefits beyond - those achieved with GLP-1RAs.6–8 The SURPASS-CVOT trial was therefore designed to rigorously test the cardiovascular safety and potential superiority of tirzepatide vs dulaglutide in patients with type 2 diabetes and established ASCVD. A major strength of this study lies in its conservative and methodologically robust design. The trial adopted a particularly stringent non-inferiority margin, with the upper limit of the 95.3% CI of the HR set at 1.05. This narrow margin substantially reduces the risk that a clinically meaningful loss in cardiovascular efficacy could be missed. In addition, the study employed a standard three-component primary endpoint—cardiovascular death, MI, or stroke—consistent with contemporary cardiovascular outcome trials, facilitating comparisons with prior GLP-1RA studies. The trial was adequately powered to detect realistic differences in efficacy, assuming a 10% lower risk for non-inferiority and a 15% lower risk for superiority. Follow-up extended to approximately four years, and event accrual was appropriate: the annualized event rate in the dulaglutide group (3.3%) was only marginally lower than anticipated, confirming effective population risk enrichment.