Real-World Comparative Effectiveness of Tirzepatide and Semaglutide for Obesity: A Multicentered Study

To compare the real-world weight loss effectiveness and safety of tirzepatide and semaglutide in patients treated for obesity, including those with prior obesity medication (OM) use.

This retrospective, multicenter study analyzed adults prescribed tirzepatide or semaglutide for weight loss across multiple US health care centers from January 1, 2021, through May 1, 2024. Total body weight loss percentage (TBWL%) was assessed at 3, 6, 9, and 12 months. Subgroup analyses were conducted by diabetes status, medication dose, and prior OM use. Safety was evaluated based on reported gastrointestinal side effects.

Among 511 patients (n= 469; 91.8% White, n= 382; 74.8% female, mean body mass index 40.0 kg/m²), tirzepatide (n=207) was associated with greater 12-month TBWL% than semaglutide (n=304) (16.6% ± 8.6% vs 13.4% ± 8.0%; P<.01). More tirzepatide users achieved greater than or equal to 15% (56.8% vs 40.7%; P=.03) and greater than or equal to 20% TBWL% (39.0% vs 22.1%; P<.01). Among patients without diabetes, tirzepatide led to significantly greater weight loss than semaglutide (18.5% ± 8.2% vs 14.2% ± 8.6%; P<.01). Prior OM use was associated with reduced weight loss in both groups (semaglutide: 10.4% vs 14.4%, tirzepatide: 16.1% vs 17.1%; P<.01). Semaglutide users reported more gastrointestinal side effects than tirzepatide users (50.7% vs 28.5%; P<.01).

In this large, real-world cohort, tirzepatide resulted in greater weight loss than semaglutide, including in patients with prior OM exposure. Both agents were generally well tolerated, although gastrointestinal side effects were more frequent with semaglutide. Further studies in more diverse populations are warranted.