[en] Several glucagon-like peptide-1 receptor agonists (GLP-1RAs) have proven their ability to reduce major adverse cardiovascular events (MACEs) among at-risk patients living with type 2 diabetes (T2D). Tirzepatide, a dual GIP/GLP-1 receptor agonist, demonstrated a better control of hyperglycaemia, body weight and several cardiovascular risk factors than pure GLP-1RAs (including semaglutide) in dedicated studies of the SURPASS programme. SURPASS CVOT has the primary objective to demonstrate, in a population with T2D and atheromatous cardiovascular disease, the non-inferiority of tirzepatide regarding both efficacy and safety compared with dulaglutide, a selective GLP-RA that has already proven a significant reduction in MACEs versus placebo in the REWIND trial. Non-inferiority was met in SURPASS CVOT (p = 0.003), but not superiority of tirzepatide compared to dulaglutide (hazard ratio [HR] 0.92; 95 % confidence interval [IC] 0.83 to 1.01; P = 0.09) regarding the primary end point (reduction in MACEs). Several secondary end points tended to favour tirzepatide versus dulaglutide, among which a reduction in the incidence of all-cause deaths after four years of median follow-up (HR 0.84 ; 95 % CI 0.75 to 0.94; exploratory analysis). SURPASS CVOT, the first and unique study that used an active comparator rather than a placebo, confirms the efficacy and safety of the dual agonist tirzepatide in patients with T2D and atheromatous cardiovascular disease.
