Meta-Analysis: Tirzepatide Produces Greater Weight Loss Than Semaglutide in People With Obesity

What the researchers found

Across seven RCTs (n=5,140), the overall placebo-subtracted weight loss was 15.0% (95% CI: -17.8 to -12.2). When broken down by drug:

- Semaglutide 2.4 mg weekly (5 studies, n=3,288): -12.9% weight loss (95% CI: -14.7 to -11.1), -9.7 cm waist circumference reduction (95% CI: -10.8 to -8.5)

- Tirzepatide 10 or 15 mg weekly (2 studies, n=1,852): -19.2% weight loss (95% CI: -22.2 to -16.2), -14.6 cm waist circumference reduction (95% CI: -15.8 to -13.4)

Adverse events were primarily gastrointestinal, mild to moderate in severity, most frequent during dose titration, and leveled off during maintenance treatment.

Why it matters

This meta-analysis provides the most comprehensive pooled comparison of the two leading incretin-based obesity treatments to date. With over 5,000 patients, it gives clinicians stronger evidence to guide treatment decisions and helps quantify the magnitude of weight loss patients can expect from each drug.

How the study worked

This was a systematic review and meta-analysis following standard methodology. From 744 identified records, seven randomized controlled trials were included — five studying semaglutide 2.4 mg and two studying tirzepatide 10 or 15 mg — all in people with obesity without diabetes. Primary outcomes were placebo-subtracted changes in body weight and waist circumference, with safety assessed across all trials.

What this study cannot tell us

The comparison between semaglutide and tirzepatide is indirect, as no head-to-head RCTs were included. Only two tirzepatide trials were available compared to five for semaglutide. All studies excluded people with diabetes, limiting generalizability. Trial durations and populations varied across studies, and long-term outcomes beyond the study periods were not assessed.

How to read the evidence

This is a systematic review and meta-analysis of randomized controlled trials — the highest level of clinical evidence. However, the comparison between drugs is indirect (no head-to-head trials), and the tirzepatide data comes from only two studies.

When this study was published

Published in 2024, this meta-analysis reflects the most current pooled evidence on semaglutide and tirzepatide for obesity at the time of publication.

The bigger picture

Incretin-based therapies have transformed obesity treatment, producing weight loss previously achievable only through surgery. This meta-analysis confirms tirzepatide's superiority over semaglutide for weight reduction, which may influence treatment algorithms and guideline development as the field continues to evolve with newer dual and triple agonists in the pipeline.

Questions still open

• Would a head-to-head randomized trial confirm tirzepatide's superiority over semaglutide for weight loss?
• How do these weight loss results translate to long-term cardiovascular and metabolic outcomes?
• What is the optimal approach for patients who do not respond adequately to one of these drugs — switching or combining?

Common questions

Read the original research

Potent incretin-based therapy for obesity: A systematic review and meta-analysis of the efficacy of semaglutide and tirzepatide on body weight and waist circumference, and safety.

Obesity reviews : an official journal of the International Association for the Study of Obesity, 25(5), e13717

Citation

Müllertz, Alberte Laura Oest; Sandsdal, Rasmus Michael; Jensen, Simon Birk Kjær; Torekov, Signe Sørensen. (2024). Potent incretin-based therapy for obesity: A systematic review and meta-analysis of the efficacy of semaglutide and tirzepatide on body weight and waist circumference, and safety.. Obesity reviews : an official journal of the International Association for the Study of Obesity, 25(5), e13717. https://doi.org/10.1111/obr.13717