Established tirzepatide for T2D. Notable for head-to-head superiority over insulin degludec.
Core trials
- SURPASS-1: tirz vs placebo
- SURPASS-2: vs sema 1.0 mg, superior A1c and weight
- SURPASS-3: vs titrated insulin degludec, superior A1c and weight, lower hypoglycemia
- SURPASS-4: vs glargine in T2D + CV risk
- SURPASS-5: tirz added to insulin glargine
- SURPASS-CVOT: tirzepatide vs dulaglutide 1.5 mg in 13,299 adults with T2D and established CV disease; non-inferior for MACE (HR 0.92; 95.3% CI 0.83 to 1.01), superiority not shown
FDA approval
Mounjaro approved 2022 for T2D. On August 27, 2026, FDA added an indication to reduce the risk of major adverse CV events in adults with T2D at high CV risk, based on SURPASS-CVOT. The CV indication applies to Mounjaro, not to Zepbound or compounded tirzepatide.
Implications
Tirzepatide superior to titrated basal insulin in T2D — meaningful change to treatment intensification choices. SURPASS-CVOT showed tirzepatide was non-inferior to dulaglutide, a GLP-1 with proven CV benefit, which led to the 2026 Mounjaro CV indication.