Tirzepatide for the treatment of obesity: Rationale and design of the SURMOUNT clinical development program.

OBJECTIVE: Obesity is a growing global concern compounded by limited availability of effective treatment options. The SURMOUNT development program aims to evaluate the efficacy and safety of tirzepatide as an adjunct to lifestyle intervention compared with placebo on chronic weight management in adults with BMI ≥ 27 kg/mwith or without type 2 diabetes. METHODS: The SURMOUNT program includes four global phase 3 trials NCT04184622 (SURMOUNT-1), NCT04657003 (SURMOUNT-2), NCT04657016 (SURMOUNT-3), and NCT04660643 (SURMOUNT-4). Participants are randomized to once-weekly subcutaneous tirzepatide versus placebo in a double-blind manner. The primary end point in all trials is the percentage change in body weight from randomization to end of treatment. Results for the primary end point for SURMOUNT-1 were published recently and results for the other trials are expected in 2023. RESULTS: Across trials, participants have a mean age of 44.9 to 54.2 years, are mostly female (50.7% to 69.7%), and have a mean BMI of 36.1 to 38.9. CONCLUSIONS: The extensive assessment of once-weekly tirzepatide in the global SURMOUNT program will detail the clinical effects of this first-in-class glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist in chronic weight management.