Introduction <p>Recent pharmacological options for weight management include the glucagon-like peptide&#xa0;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.</p> Methods <p>Based on a systematic literature review (SLR) and Bayesian network meta-analysis (NMA), the efficacy and safety of semaglutide 2.4&#xa0;mg, liraglutide 3&#xa0;mg and tirzepatide 5, 10 and 15&#xa0;mg were compared in adults without type&#xa0;2 diabetes, and with either obesity (body mass index [BMI] ≥ 30&#xa0;kg/m<sup>2</sup>) or overweight (BMI ≥ 27&#xa0;kg/m<sup>2</sup>) with ≥ 1 obesity-related complication.</p> Results <p>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&#xa0;mg versus semaglutide: including percentage weight reduction (−&#xa0;12.86% for tirzepatide 10&#xa0;mg and −&#xa0;13.95% for tirzepatide 15&#xa0;mg versus liraglutide; −&#xa0;4.85% and − 6.26% versus semaglutide) and waist circumference (−&#xa0;11.79&#xa0;cm and − 12.30&#xa0;cm versus liraglutide; −&#xa0;4.81&#xa0;cm and −&#xa0;5.32&#xa0;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.</p> Conclusion <p>In this NMA, tirzepatide 10 and 15&#xa0;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.</p>

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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

  • Andreea Ciudin,
  • Helene Sapin,
  • Ludi Fan,
  • Georgios K. Dimitriadis,
  • Sarah Zimner-Rapuch,
  • Tristan Curteis,
  • Laura J. Clark,
  • Manon Rubinstein,
  • Erin Johansson

摘要

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/m2) or overweight (BMI ≥ 27 kg/m2) with ≥ 1 obesity-related complication.

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.