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Comparative Efficacy of Tirzepatide Versus Semaglutide for Weight Loss in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis of Head-to-Head Studies.

Giovanna Pagani Paccola·Roberta Fernandes de Oliveira·Matheus Menão Mochetti·Fernanda Pataro Marsola Razera·Rafael Vecchi·Renan Canale Peres Montanher
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Abstract

This systematic review and meta-analysis aimed to compare&#xa0;the efficacy and safety of tirzepatide versus semaglutide for weight reduction in adults with overweight or obesity. We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with &#x2265;&#x2009;24&#x2009;weeks of follow-up. The primary outcome was percentage weight change from baseline. Secondary outcomes included absolute weight change, weight-loss thresholds, HbA1c and safety outcomes. Ten studies including 41&#x2009;381 participants were analysed. Tirzepatide was associated with greater percentage weight reduction than semaglutide (MD -4.28 percentage points; 95% CI -5.28 to -3.28; p&#x2009;<&#x2009;0.00001) and greater absolute weight loss (MD -4.43&#x2009;kg; 95% CI -5.56 to -3.30; p&#x2009;<&#x2009;0.00001). Tirzepatide was also associated with a higher likelihood of achieving &#x2265;&#x2009;10%, &#x2265;&#x2009;15% and &#x2265;&#x2009;20% weight loss, with no difference at &#x2265;&#x2009;5%. HbA1c reduction was greater with tirzepatide (MD -0.29%; p&#x2009;=&#x2009;0.0002). Subgroup analyses by study design and type 2 diabetes status yielded consistent findings. There was no significant difference in treatment discontinuation due to adverse events (RR 1.28; p = 0.54), whereas serious adverse events were more frequent with tirzepatide (RR 1.83; p&#x2009;=&#x2009;0.007). Overall and gastrointestinal adverse events were similar between groups. Tirzepatide was associated with greater weight reduction, greater glycaemic benefit and a higher likelihood of achieving weight-loss thresholds than semaglutide, but with a higher risk of serious adverse events.

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HumansTirzepatideSemaglutideWeight LossObesityGlucagon-Like PeptidesOverweightTreatment OutcomeAdultRandomized Controlled Trials as TopicAnti-Obesity AgentsFemaleMaleobesitysemaglutidetirzepatideweight lossJournal ArticleSystematic ReviewMeta-AnalysisComparative Study

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Giovanna Pagani Paccola, Roberta Fernandes de Oliveira, Matheus Men&#xe3;o Mochetti, Fernanda Pataro Marsola Razera, Rafael Vecchi, Renan Canale Peres Montanher. 2026. Comparative Efficacy of Tirzepatide Versus Semaglutide for Weight Loss in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis of Head-to-Head Studies.. https://doi.org/10.1111/cob.70111

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Adult subjectAnti-Obesity Agents subjectComparative Study subjectFemale subjectHumans subjectJournal Article subjectMale subjectMeta-Analysis subjectObesity subjectOverweight subjectSystematic reviews study

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