Abstract

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. 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. 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. 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. Obesity management is crucial for reducing the health risks associated with obesity, and comprises of behavioural interventions, psychological support, dietary changes and physical activity programs. Medications may also be prescribed, or surgical options may also be considered. Three such medications for weight management are injectable weekly treatments tirzepatide and semaglutide, or daily liraglutide, which help to control appetite by prolonging patients’ feeling of fullness. Because there are no clinical trials directly comparing tirzepatide and liraglutide, and no trials comparing all three medications, this study aimed to indirectly compare the effectiveness and safety of tirzepatide, semaglutide and liraglutide for weight management in patients without type 2 diabetes, who also have obesity or overweight. A systematic review of literature identified all published clinical trials reporting on tirzepatide, semaglutide and liraglutide. Following strict eligibility criteria, six suitable randomised controlled trials were chosen for analysis. These studies had similar designs and patients, making it possible to compare their results meaningfully. Tirzepatide demonstrated improved results across various outcomes, including weight loss and cardiometabolic health factors compared with liraglutide. Compared with semaglutide, the higher doses of tirzepatide demonstrated consistent improvements in weight reduction and cardiometabolic health factors, whilst the lower dose was broadly comparable with semaglutide. The safety profile of tirzepatide was generally similar to both liraglutide and semaglutide. Overall, the analysis supports the clinical effectiveness and safety of tirzepatide compared with liraglutide and semaglutide in weight reduction and other clinical outcomes associated with weight management in patients with obesity or overweight.