Analysis ranks tirzepatide doses above semaglutide for average weight loss

A network meta-analysis published in September 2025 concluded that tirzepatide produced greater average weight loss than semaglutide in adults with obesity who do not have diabetes, with the largest effects at the highest doses studied — and the highest odds of stopping treatment because of side effects at those same doses ^[1].

Tirzepatide is sold as Mounjaro and Zepbound; semaglutide is sold as Ozempic, Wegovy and Rybelsus. The analysis pooled eight randomized controlled trials with 7,179 participants and compared four tirzepatide doses (5 mg, 10 mg, 15 mg and maximum tolerated dose) and two semaglutide doses (2.4 mg and maximum tolerated dose) against placebo ^[1]. Tirzepatide is a dual GLP-1 and GIP receptor agonist; semaglutide is a GLP-1 receptor agonist ^[1].

The main results, expressed as mean differences in body weight versus placebo, were: tirzepatide at maximum tolerated dose, −20.90% (95% confidence interval −24.93 to −16.87); tirzepatide 15 mg, −18.08% (−20.38 to −15.78); tirzepatide 10 mg, −14.93% (−17.23 to −12.63); semaglutide at maximum tolerated dose, −14.40% (−19.82 to −8.98); semaglutide 2.4 mg, −11.78% (−13.91 to −9.64); and tirzepatide 5 mg, −11.49% (−14.65 to −8.34) ^[1]. Every active treatment did significantly better than placebo ^[1].

The confidence interval for semaglutide at its maximum tolerated dose was the widest of the six, running from −19.82% to −8.98%, and it overlaps the estimates for several tirzepatide doses ^[1]. The authors wrote that direct comparisons across the two drugs' dose ranges were lacking, which means the ranking rests on indirect comparisons built from trials that tested each drug against placebo rather than against each other ^[1].

Waist circumference and the share of participants losing at least 15% of body weight followed the same dose-related pattern ^[1]. The authors rated the certainty of the evidence for that 15% threshold as high for most interventions, and moderate for semaglutide at maximum tolerated dose and tirzepatide 5 mg ^[1].

On safety, the highest odds of discontinuing treatment because of adverse events were seen with semaglutide at maximum tolerated dose (odds ratio 7.36; 95% CI 2.56 to 21.15) and tirzepatide at maximum tolerated dose (odds ratio 5.56; 95% CI 2.28 to 13.58) ^[1]. Gastrointestinal side effects were more common with higher-dose regimens ^[1]. The authors reported no publication bias ^[1].

Why it matters for patients

Dose is not a detail. Tirzepatide 5 mg ranked below semaglutide 2.4 mg for average weight loss in this analysis, while tirzepatide 15 mg ranked above every semaglutide dose studied ^[1]. Higher average weight loss at the top doses came with more gastrointestinal side effects and higher odds of stopping treatment ^[1].

The ranking describes group averages from pooled trials, not what any one person will experience. The analysis included only non-diabetic adults with obesity, so its results do not describe people with type 2 diabetes ^[1]. And because the drug-to-drug comparison is indirect, it is not the same as a head-to-head trial result ^[1].

Several practical questions are outside this analysis. It did not report costs, insurance coverage, cardiovascular outcomes, or how well weight loss held up after treatment stopped ^[1]. What those numbers mean for an individual's coverage or prescription has not been disclosed ^[1].

What happens next

The analysis names no follow-up studies or timelines, and no dates for further results have been reported ^[1]. Direct comparisons of tirzepatide and semaglutide across their dose ranges were still lacking at the time of publication, according to the authors ^[1].