TOPLINE

Among adults with overweight or obesity, tirzepatide was associated with greater weight reduction and glycemic improvement than semaglutide but was also linked to a higher risk for serious adverse events, according to a meta-analysis of head-to-head studies.

METHODOLOGY

• Incretin-based agents such as tirzepatide and semaglutide have emerged as highly effective options for weight loss, but direct head-to-head comparisons of their efficacy and safety in adults with overweight or obesity remain limited.
• Researchers conducted a systematic review and meta-analysis of 10 head-to-head studies (three randomized controlled trials and seven retrospective cohort studies) to compare tirzepatide and semaglutide in 41,381 adults with overweight or obesity.
• Studies were conducted across multiple geographic regions, with intervention follow-up durations ranging from 24 weeks to 72 weeks. Studies were required to evaluate adults with a BMI ≥ 25 and exclude clinically distinct populations such as those with type 1 diabetes, prior bariatric surgery, or active malignancy.
• Tirzepatide and semaglutide were administered as once-weekly subcutaneous injections using study-specific fixed-dose, dose-escalation, maximum tolerated dose, or variable real-world dosing regimens; doses ranged from 2.5 mg to 15 mg for tirzepatide and from 0.25 mg to 2.4 mg for semaglutide.
• The primary outcome was the mean percentage change in body weight from baseline; secondary outcomes included absolute weight change (kg), reduction in A1c levels, and safety outcomes.

TAKEAWAY

• Tirzepatide was associated with greater weight loss than semaglutide, both as a percentage of body weight (mean difference [MD], −4.28 percentage points; 10 studies) and in absolute terms (MD, −4.43 kg; eight studies). 
• A seven-study analysis found that patients treated with tirzepatide were more likely to reach ≥ 10% (risk ratio [RR], 1.43), ≥ 15% (RR, 1.85), and ≥ 20% (RR, 2.03) weight loss than those on semaglutide, with no significant difference at the ≥ 5% threshold. 
• Tirzepatide was also associated with a greater reduction in A1c levels (MD, −0.29 percentage points; 95% CI, −0.44 to −0.14; five studies) than semaglutide. 
• Serious adverse events were significantly more frequent with tirzepatide than with semaglutide (experienced by 5.7% vs 2.9% of patients; RR, 1.83; three studies); however, treatment discontinuation rates due to adverse events did not differ significantly between the groups. 

IN PRACTICE

"Among adults with overweight or obesity, tirzepatide is associated with greater weight reduction and modestly greater glycaemic improvement compared with semaglutide, although these benefits may be accompanied by a higher risk of serious adverse events. These findings highlight the need to balance efficacy and tolerability when selecting incretin-based therapies," the authors wrote.

SOURCE

This study was led by Giovanna Pagani Paccola, Faculdade de Medicina de Jaú, Universidade do Oeste Paulista, Jaú, São Paulo, Brazil. It was published online in Clinical Obesity.

LIMITATIONS

Large observational cohorts accounted for much of the total sample, and residual confounding could not be ruled out. Substantial heterogeneity was found across several efficacy outcomes. In addition, the maximum follow-up of 72 weeks limited the evaluation of long-term weight-loss durability and rare safety events. 

DISCLOSURES

The article processing charge was funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.