Clinical Implications of The Direct Comparison of Dulaglutide Versus Tirzepatide

It is unclear which incretin-based therapy has the best impact on reduction of cardiovascular (CV) outcomes and mortality. The SURPASS-CVOT trial was the first randomized trial to directly compare the effects of 2 incretin-based therapies, tirzepatide and dulaglutide, on such outcomes in patients with type 2 diabetes and atherosclerotic CV disease. After 4 years of follow-up, tirzepatide was non-inferior to dulaglutide in incidence of a composite of death from CV causes, myocardial infarction (MI), or stroke (the primary outcome). While statistical superiority of tirzepatide over dulaglutide was not achieved, there was a trend toward decrease incidence of individual CV events with tirzepatide and a remarkable 16% decrease in all-cause mortality versus dulaglutide. Tirzepatide was more effective than dulaglutide in lowering body weight, glycated hemoglobin levels and systolic blood pressure. Gastrointestinal (GI) adverse effects were more common with tirzepatide (42.5%) versus dulaglutide (35.9%). The main limitation of the SURPASS-CVOT trial is the comparison of maximum doses of tirzepatide (15mg) with sub-maximal doses of dulaglutide (1.5 mg), but this limitation is unlikely to significantly change the results of the study. Overall, tirzepatide is preferred over dulaglutide in patients with high CV risk.