Tirzepatide outscores Semglutide for weight loss in head to head comparison

Obesity treatment widely ranges from lifestyle changes to many drugs. Obesity is now recognized as a disease and treatments that induce short-term weight loss often fail over time. Effective treatments are needed to address the complex and persistent hormonal, metabolic and neurochemical adaptations; poor adherence; and persistence experienced by those living with obesity.

The study in Diabetes, Obesity and Metabolism aimed to use indirect treatment comparisons (ITCs) using placebo as the common comparator to provide evidence on the comparative efficacy of tirzepatide 10 and 15 mg versus semaglutide 2.4 mg.

The study found that this analysis showed greater weight loss with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg.

Researchers used SURMOUNT-1 and STEP 1 trial data, mean percentage change in body weight from baseline and odds ratio (OR) of achieving 5% or greater weight loss were compared between tirzepatide 10 and 15 mg at week 72 and semaglutide 2.4 mg at week 68 using matching-adjusted indirect comparison of the efficacy estimand. Sensitivity analyses were completed using different methods, including the Bucher method, also using different estimands and/or time points.

The key findings of the study are

• Greater reductions in percentage change in body weight were observed with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg (tirzepatide 10 mg mean difference: −4.67% [95% CI −5.91%, −3.43%]; tirzepatide 15 mg mean difference: −5.92% [95% CI −7.16%, −4.68%]; both P < .001).

• Similarly, more participants achieved 5% or greater weight loss with tirzepatide 10 mg (OR 2.61 [95% CI 1.48, 4.57]; P < .001) and 15 mg (OR 2.75 [95% CI 1.57, 4.81]; P < .001) compared with semaglutide 2.4 mg.

• All sensitivity analyses were consistent, except for an OR of achieving 5% or greater weight loss with tirzepatide 10 mg using the Bucher method to analyse the treatment regimen estimand (P = .074).

The researchers added currently there are no direct comparisons of tirzepatide and semaglutide for weight management. Using the matching-adjusted indirect treatment comparison method to compare the efficacy of tirzepatide and semaglutide for chronic weight management, this analysis showed greater weight loss with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg.

Reference: Carel W. le Roux MD, Emily R. Hankosky PhD,; Tirzepatide 10 and 15 mg compared with semaglutide 2.4 mg for the treatment of obesity: An indirect treatment comparison; 21 June 2023, Diabetes, Obesity and Metabolism; DOI: https://doi.org/10.1111/dom.15148.