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Review
. 2025 Jun 15;17(6):e86080.
doi: 10.7759/cureus.86080. eCollection 2025 Jun.

Tirzepatide Versus Semaglutide for Weight Loss in Overweight and Obese Adults: A Systematic Review and Meta-Analysis of Direct Comparative Studies

Nazish Munawar  1 , Aakash Mahato  2 , Anurag Rawat  3 , Fahad Shaukat Gill  4 , Daksh Kumar  5 , Susant Katwal  6 , Calvin R Wei  7 , Neelum Ali  8
Affiliations
Review

Tirzepatide Versus Semaglutide for Weight Loss in Overweight and Obese Adults: A Systematic Review and Meta-Analysis of Direct Comparative Studies

Nazish Munawar et al. Cureus. .

Abstract

This systematic review and meta-analysis compared the weight loss efficacy of tirzepatide versus semaglutide in overweight and obese adults through direct comparative studies. We systematically searched PubMed, Excerpta Medica database (EMBASE), Web of Science, and Cochrane Library databases from inception to April 25, 2025, identifying studies that directly compared tirzepatide and semaglutide for weight management. Inclusion criteria encompassed randomized controlled trials and observational studies reporting percentage change in body weight from baseline. Seven studies totaling 28,980 participants were included, comprising five observational studies and two randomized controlled trials with follow-up durations ranging from six to 12 months. Data analysis was performed using Review Manager 5.4.1 (The Cochrane Collaboration, London, UK) with random-effects models. Results demonstrated that tirzepatide was significantly superior to semaglutide in achieving weight reduction. The pooled analysis showed greater weight loss with tirzepatide compared to semaglutide (standardized mean difference: 0.75, 95% CI: 0.52 to 0.92). At six months, tirzepatide achieved significantly greater weight reduction than semaglutide (mean difference: 1.33, 95% CI: 0.58 to 2.08). Additionally, participants receiving tirzepatide had significantly higher odds of achieving at least 10% weight loss compared to those receiving semaglutide (OR: 0.21, 95% CI: 0.06 to 0.78). High heterogeneity was observed across studies (I² > 90%). This meta-analysis provides evidence that tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonist, demonstrates superior weight loss efficacy compared to semaglutide in overweight and obese populations. These findings support tirzepatide as a more effective pharmacological option for weight management, though further long-term head-to-head trials are needed to confirm sustained benefits and safety profiles.

Keywords: meta-analysis; obesity; semaglutide; tirzepatide; weight loss.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. PRISMA flowchart of study selection
PRISMA: Preferred Reporting Items for Systematic reviews and Meta-Analyses
Figure 2
Figure 2. Comparison of the change in weight between the two groups
[14-20]
Figure 3
Figure 3. Comparison of change in weight between the two groups (at six months)
[16,18,20]
Figure 4
Figure 4. Forest plot comparing the number of subjects with at least 10% weight loss
[15,18-20]
See this image and copyright information in PMC

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