Tirzepatide for reduction of morbidity and mortality in adults with obesity: rationale and design of the SURMOUNT-MMO trial.

OBJECTIVE: Obesity is a major cause of morbidity and mortality worldwide. Tirzepatide is a glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist providing substantial weight reduction and metabolic benefits both in type 2 diabetes and obesity. We hypothesized that tirzepatide can improve morbidity and mortality in adults with obesity or overweight but without diabetes. METHODS: SURMOUNT-MMO is a randomized, double-blind, event-driven trial to investigate the impact on morbidity and mortality with once-weekly tirzepatide compared with placebo in adults living with obesity, without diabetes, and with, or at risk of, cardiovascular disease. The primary endpoint is time to first occurrence of a five-component composite outcome of nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, heart failure events, or death from any cause. RESULTS: The trial will enroll ~15,000 participants aged ≥40 from 664 sites across 27 countries with BMI ≥27.0 kg/m and either established cardiovascular disease or multiple cardiovascular risk factors. CONCLUSIONS: SURMOUNT-MMO will provide evidence of the clinical benefits of tirzepatide on multiple outcomes among individuals with overweight or obesity but without diabetes. This is the first outcome trial of an incretin medication that assesses both primary and secondary cardiovascular disease prevention.