Comparison of Clinical Efficacy and Safety of Tirzepatide, Liraglutide and Semaglutide in Patients with Obesity and Without T2D: A Bayesian Network Meta-Analysis of Randomised Controlled Trials

Mar 13, 2026Advances in therapy

Comparing the effectiveness and safety of Tirzepatide, Liraglutide, and Semaglutide for treating obesity without diabetes

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Abstract

Tirzepatide 10 mg and 15 mg were associated with a 12.86% and 13.95% greater weight reduction compared to liraglutide.

Tirzepatide doses were linked to statistically significant improvements in weight reduction and waist circumference compared to liraglutide.
Percentage weight reduction for tirzepatide 10 mg and 15 mg was -12.86% and -13.95% versus liraglutide, and -4.85% and -6.26% versus semaglutide.
Waist circumference reductions were -11.79 cm and -12.30 cm for tirzepatide compared to liraglutide, and -4.81 cm and -5.32 cm compared to semaglutide.
All tirzepatide doses showed statistically greater improvements in triglycerides and diastolic blood pressure compared to liraglutide.
There were generally comparable improvements in other glycaemic, lipid, and blood pressure parameters across all interventions.
All treatments demonstrated a comparable safety profile.

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INTRODUCTION: Recent pharmacological options for weight management include the glucagon-like peptide 1 (GLP-1) receptor agonists semaglutide and liraglutide, and the glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide, but head-to-head comparisons of all three of these interventions are lacking.

METHODS: Based on a systematic literature review (SLR) and Bayesian network meta-analysis (NMA), the efficacy and safety of semaglutide 2.4 mg, liraglutide 3 mg and tirzepatide 5, 10 and 15 mg were compared in adults without type 2 diabetes, and with either obesity (body mass index [BMI] ≥ 30 kg/m) or overweight (BMI ≥ 27 kg/m) with ≥ 1 obesity-related complication. 2 2

RESULTS: Following a stringent heterogeneity assessment, six of 42 randomised controlled trials identified in the SLR were included in the NMA. Efficacy estimand results showed all tirzepatide doses were associated with statistically greater improvements in weight reduction outcomes versus liraglutide, and for tirzepatide 10 and 15 mg versus semaglutide: including percentage weight reduction (- 12.86% for tirzepatide 10 mg and - 13.95% for tirzepatide 15 mg versus liraglutide; - 4.85% and - 6.26% versus semaglutide) and waist circumference (- 11.79 cm and - 12.30 cm versus liraglutide; - 4.81 cm and - 5.32 cm versus semaglutide). All tirzepatide doses were associated with statistically greater improvements in triglycerides and diastolic blood pressure versus liraglutide, and generally comparable improvements in other glycaemic, lipid and blood pressure parameters versus liraglutide and semaglutide. All interventions had a comparable safety profile.

CONCLUSION: In this NMA, tirzepatide 10 and 15 mg were associated with improved efficacy versus liraglutide, improved or comparable efficacy versus semaglutide, and all interventions had a generally comparable safety profile for achieving weight reduction and reducing cardiometabolic risk factors among patients with obesity or overweight.

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Comparison of Clinical Efficacy and Safety of Tirzepatide, Liraglutide and Semaglutide in Patients with Obesity and Without T2D: A Bayesian Network Meta-Analysis of Randomised Controlled Trials

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