Network meta-analysis ranks tirzepatide doses above semaglutide for weight loss
A pooled analysis of eight trials in 7,179 people found tirzepatide at its highest doses produced more weight loss than semaglutide, but both carried higher odds of stopping treatment due to side effects at top doses.
A new network meta-analysis pooled data from eight randomized controlled trials involving 7,179 non-diabetic adults with obesity to compare tirzepatide and semaglutide head to head across dose levels [1]. The study, published on PubMed, found that tirzepatide at its maximum tolerated dose produced the largest average weight loss, with a mean difference of -20.90% compared with placebo [1].
Tirzepatide 15 mg came in second, at -18.08% versus placebo, followed by tirzepatide 10 mg at -14.93% [1]. Semaglutide at its maximum tolerated dose showed a mean difference of -14.40%, while the standard 2.4 mg dose of semaglutide showed -11.78% [1]. Tirzepatide 5 mg, the lowest dose studied, came in at -11.49%, similar to semaglutide's standard dose [1]. All active treatments beat placebo by a wide margin [1].
The analysis also looked at waist circumference and the odds of losing at least 15% of body weight, and found the same pattern: higher doses of tirzepatide ranked above semaglutide doses on both measures [1]. Researchers rated the certainty of evidence for the 15% weight-loss threshold as high for most doses, though moderate for semaglutide's maximum tolerated dose and tirzepatide 5 mg [1].
The tradeoff showed up in side effects. The highest odds of stopping treatment because of adverse events were seen with semaglutide at its maximum tolerated dose, with an odds ratio of 7.36, and tirzepatide at its maximum tolerated dose, with an odds ratio of 5.56, both compared with placebo [1]. Gastrointestinal side effects were more common with higher-dose regimens across both drugs [1]. The study authors reported no evidence of publication bias in their data [1].
Why it matters for patients
This analysis adds to a growing body of evidence suggesting tirzepatide, sold as Mounjaro or Zepbound, may produce greater average weight loss than semaglutide, sold as Ozempic, Wegovy, or Rybelsus, when both are pushed to their highest tolerated doses [1]. But the study's own authors note this comes
Sources
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