Tirzepatide proves superior to semaglutide in both body weight reduction and improvement of glycaemic indices, a 2026 network meta-analysis has found.
GLP-1 Use in Diabetes Treatment
Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1), and tirzepatide is a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist (GIP/GLP-1).
They are among the leading options for obesity treatment. Risks associated with obesity are primarily related to metabolic disorders, which contribute to the development of Type 2 diabetes mellitus and other diseases including osteoarthritis and sleep apnoea.
Tirzepatide Versus Semaglutide
Pairwise comparisons in the network meta-analysis were conducted using a frequentist approach in a total of 28 randomised controlled trials, examining more than 34,300 patients with obesity. Tirzepatide or semaglutide was compared with placebo, as well as tirzepatide versus semaglutide. They were analysed at their maximum doses (1 mg and 2.4 mg, respectively).
Tirzepatide was superior to semaglutide in percentage weight reduction with a mean difference (MD) of 6.1%. It also performed better in absolute weight loss, with an MD of 4.55 kg, and waist circumference reduction, with an MD of 2.89 cm.
Tirzepatide was also more effective than semaglutide in reducing glycated haemoglobin and blood glucose, proving favourable in managing glycaemic parameters.
Limitations
A key limitation was the rarity of trials directly comparing tirzepatide and semaglutide, leading to indirect comparisons.
Most included studies also had relatively short follow-up durations, limiting robust long-term assessments of sustained weight loss and remission of obesity-related comorbidities.
Implications for Type 2 Diabetes Treatment
Participants without Type 2 diabetes have previously demonstrated greater relative weight loss with tirzepatide compared with those with diabetes. Individuals with more severe obesity often exhibit larger absolute reductions in body weight with both tirzepatide and semaglutide.
Although the maximum doses produced clinically meaningful results, lower doses than maximum have also demonstrated efficacy superior to conventional obesity treatment.
Hence tirzepatide might be preferable for individuals with severe obesity or Type 2 diabetes requiring rapid and intense metabolic improvement. Semaglutide remains an appropriate first-line option when cost, availability, or tolerability restricts the use of tirzepatide.
Reference
Bernardi J C et al. Who wins the battle against obesity? A network meta-analysis comparing tirzepatide and semaglutide. J Diabetes. 2026;18(2):DOI:10.1111/1753-0407.70192.
