OBJECTIVES: SURMOUNT-1 demonstrated significant weight reduction and improvement in cardiometabolic risk factors with tirzepatide treatment, but data beyond 72 weeks are currently unavailable for people with overweight and obesity without T2DM. This study uses a patient-level simulation (PLS) to estimate long-term clinical outcomes with tirzepatide versus relevant comparators.

METHODS: A PLS was implemented in the discretely-integrated condition-event (DICE) framework, which considers patient heterogeneity and event history. NHANES data, filtered to match FDA guidance for obesity treatment excluding patients with T2DM, supplied baseline patient characteristics. The model used published data to simulate the impact of tirzepatide and key comparators on BMI. Simulated metabolic factor (i.e., BMI, HDL, SBP, and fasting plasma glucose) trajectories were inputs to published risk equations that estimate risk of key obesity-related complications: cardiovascular events (Framingham 10-year risk estimate) and onset of type 2 diabetes (T2DM; Framingham Offspring study). Health-related quality of life was linked to BMI and complications over time. All comparators were modeled at the highest indicated dose.

RESULTS: Versus semaglutide, phentermine/topiramate, naltrexone/buproprion, and lifestyle modification (LSM), the model predicted tirzepatide increases life expectancy by 0.06, 0.22, 0.30, and 0.29 years, and increases quality-adjusted life expectancy by 0.17, 0.59, 0.86, and 0.90 QALYs, respectively. Tirzepatide is predicted to decrease event rates and increase average time to onset of modeled obesity-related complications. Specifically, the model predicted tirzepatide reduced the percentage of patients with any cardiovascular event compared to semaglutide, phentermine/topiramate, naltrexone/buproprion and LSM by 0.6%, 3.3%, 3.4% and 3.2% respectively, and delayed time to onset of T2DM by 0.89, 2.39, 4.26, and 4.35 years, respectively. A similar pattern of benefit is seen for lower tirzepatide doses.

CONCLUSIONS: Long-term projections using SURMOUNT-1 data in a validated model showed people with overweight and obesity treated with tirzepatide are likely to have longer life expectancy, experience improved quality-of-life, and decreased incidence of obesity-related complications.