SURMOUNT-MMO (cardiovascular outcomes in chronic weight management)
Trial: A randomized, double-blind, placebo-controlled cardiovascular outcomes trial of tirzepatide for the reduction of MACE in adults with obesity and established cardiovascular disease (NCT05556512).
- Population: Adults aged ≥ 40 with BMI ≥ 27 and established CVD (prior MI, ischemic stroke, or peripheral arterial disease).
- Primary endpoint: Time to first occurrence of MACE-3 (cardiovascular death, non-fatal MI, non-fatal stroke).
- Design parallel: Modeled after Novo Nordisk's SELECT trial (semaglutide 2.4 mg in non-diabetic obesity + CVD), which demonstrated a 20% relative reduction in MACE-3 (NEJM 2023, PMID 37952131).
- Expected readout: Late 2027.
SURPASS-CVOT (cardiovascular outcomes in type 2 diabetes)
Trial: A randomized, active-controlled cardiovascular outcomes trial of tirzepatide vs dulaglutide in adults with type 2 diabetes and high cardiovascular risk (NCT04255433).
- Population: Adults with type 2 diabetes and established CVD or multiple CVD risk factors.
- Primary endpoint: Time to first MACE-3.
- Active comparator: Dulaglutide (Trulicity®), which itself demonstrated MACE benefit in REWIND (Lancet 2019).
- Expected readout: 2025–2026 (data presentation timing pending).
Current cardiovascular evidence base
As of June 2026, tirzepatide has demonstrated weight loss, A1C reduction, blood pressure reduction, and improvements in lipid profile and inflammatory markers in the SURMOUNT and SURPASS programs — all surrogate cardiovascular risk markers. The definitive MACE-reduction evidence is pending the SURMOUNT-MMO and SURPASS-CVOT readouts. The most relevant approved cardiovascular label currently belongs to semaglutide: Wegovy is FDA-approved (March 2024) for reduction of cardiovascular events in non-diabetic adults with overweight/obesity + established CVD based on SELECT.
Implications for prescribing today
- For adults with type 2 diabetes + CVD: semaglutide (Ozempic) and dulaglutide both have demonstrated MACE benefit. Tirzepatide is approved for type 2 diabetes (Mounjaro) but has not yet demonstrated MACE benefit in a completed CVOT.
- For non-diabetic adults with obesity + CVD: only semaglutide 2.4 mg (Wegovy) has demonstrated MACE benefit and a corresponding FDA label (March 2024).
- For chronic weight management without established CVD: tirzepatide demonstrates the largest mean weight loss (20.9% at 15 mg / 72 weeks, SURMOUNT-1) among currently available GLP-1 and GIP/GLP-1 receptor agonists.