Tirzepatide leads to greater weight loss than semaglutide among adults with obesity

1. In this randomized controlled trial, among adults with obesity, it was found that tirzepatide resulted in a significantly greater reduction in body weight and waist circumference than semaglutide.

2. Adverse events led to treatment discontinuation more often in the semaglutide group than in the tirzepatide group.

Evidence Rating Level: 1 (Excellent)

Study Rundown: There is currently a new generation of highly effective medications for the management of obesity, which includes tirzepatide, a long-acting glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, and semaglutide, a long-acting GLP-1 receptor agonist. Both medications result in clinically meaningful weight reductions by decreasing appetite and regulating food-related behaviors. In comparing the two agents, it has been hypothesized that the dual agonism of tirzepatide will contribute to a greater weight reduction than the monoagonism of semaglutide. The present trial assessed the efficacy and safety of tirzepatide compared with semaglutide for weight loss among adults with obesity. Tirzepatide was found to be superior to semaglutide with respect to reduction in both body weight and waist circumference. Additionally, with regard to safety, the most frequently reported adverse events were gastrointestinal in both groups, but led to treatment discontinuation more often in the semaglutide group compared with the tirzepatide group. The trial was limited by its lack of blinding, which may have led to inadvertent bias during the study process. Nevertheless, these findings show that medications with dual-agonist activity, such as tirzepatide, may achieve greater weight reduction compared to monoagonist agents.

Click to read the study in NEJM

In-Depth [randomized controlled trial]: This phase three, multicenter, randomized controlled trial compared the efficacy and safety of tirzepatide for weight loss with that of semaglutide among adults with obesity. Adults 18 years of age or older, with a body-mass index (BMI) of 30 or higher or a BMI of 27 or higher and at least one prespecified obesity-related complication, who reported at least one unsuccessful dietary effort for weight reduction, were included. Participants were randomly assigned in a 1:1 ratio to receive tirzepatide or semaglutide. The primary efficacy outcome was the percent change in body weight from baseline to week 72. A total of 750 participants were included in the study, with 374 assigned to the tirzepatide group and 376 to the semaglutide group. The mean percent change in body weight from baseline to week 72 was -20.2% in the tirzepatide group (95% Confidence Interval [CI], -21.4 to -19.1) compared with -13.7% in the semaglutide group (95% CI, -14.9 to -12.6). Thus, tirzepatide was found to be superior to semaglutide with respect to weight reduction (estimated treatment difference, -6.5 percentage points; 95% CI, -8.1 to -4.9; P<0.001). Furthermore, more participants in the tirzepatide group had reductions in body weight of at least 10%, 15%, 20%, and 25% compared to participants treated with semaglutide (p<0.001). Tirzepatide was also superior to semaglutide with respect to reduction in waist circumference, with the mean change in waist circumference from baseline to week 72 being -18.4 cm in the tirzepatide group (95% CI, -19.6 to -17.2) compared with -13.0 cm in the semaglutide group (95% CI, -14.3 to -11.7). Finally, with regards to safety, gastrointestinal adverse events were the most common, were predominantly mild to moderate in severity, and led to treatment discontinuation more often with semaglutide compared with tirzepatide. In summary, tirzepatide was found to be both safe and more effective for weight loss compared with semaglutide among adults with obesity.

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