TOPLINE:
All FDA-approved GLP-1-based therapies for patients with obesity but not type 2 diabetes significantly reduced body weight compared with placebo, with the highest doses of the dual agonist tirzepatide producing the greatest weight loss, a network meta-analysis has found.
METHODOLOGY:
- The GLP-1 s liraglutide and semaglutide and the dual GIP/GLP-1 receptor agonist tirzepatide are approved by the FDA for chronic weight management in adults without diabetes, and researchers sought to compare their effectiveness in this patient population.
- They conducted a systematic review and network meta-analysis (NMA) and identified 15 phase 3 randomized controlled trials involving 14,059 adults with overweight or obesity but without diabetes. Three trials didn’t report measures of variability and were excluded from the primary NMA, which as a result involved 12 trials with 11, 183 participants.
- Eligible studies enrolled adults (aged ≥ 18 years) who had received either of the following eight interventions: placebo, 3 mg liraglutide, 2.4 mg semaglutide, 50 mg semaglutide, and tirzepatide (5, 10, and 15 mg), as well as pooled doses of 10-15 mg tirzepatide.
- The treatment duration across trials ranged from 48-104 weeks, and most studies were conducted across multiple countries.
- The primary outcome was the mean difference (MD) in the percentage change in body weight from baseline.
TAKEAWAY:
- The primary NMA found that all FDA-approved agents reduced body weight compared with placebo, with the largest reduction occurring with tirzepatide at 10-15 mg pooled (MD, -20.06), followed by 15 mg tirzepatide (MD, -18.07), 10 mg tirzepatide (MD, -14.89), 2.4 mg semaglutide (MD, -13.39), 50 mg semaglutide (MD, -12.7), 5 mg tirzepatide (MD, -11.48), and 3 mg liraglutide (MD, -5.24).
- Tirzepatide was associated with an increased risk for any adverse event — including nausea, vomiting, diarrhea, and constipation — compared with placebo across all doses: 5 mg (risk ratio [RR], 1.14), 10 mg (RR, 1.13), and 15 mg (RR, 1.13).
- For serious adverse events, only 3 mg liraglutide (RR, 1.31) and 2.4 mg semaglutide (RR, 1.41) showed a higher risk than placebo. No tirzepatide dose was associated with a statistically significant increase.
IN PRACTICE:
“Higher doses of tirzepatide were associated with the largest reductions in body weight among adults with overweight or obesity without diabetes, followed by semaglutide and liraglutide,” the authors wrote. “In clinical practice, treatment selection should balance comparative efficacy with tolerability, accessibility, affordability, and anticipated adherence to optimize weight management outcomes.”
SOURCE:
The study, led by Michael Lim, University of Georgia College of Pharmacy in Athens, was published online in Obesity.
LIMITATIONS:
Results are based primarily on indirect comparisons, and the presence of substantial between-study heterogeneity may have introduced potential for bias. Cardiovascular outcomes, cost-effectiveness, and patient-reported outcomes were not systematically assessed. Restricting inclusion to English-language publications may have introduced language bias and limited the capture of relevant evidence published in other languages. Participants were primarily White women aged 35-54 years, limiting generalizability to other populations.
DISCLOSURES:
The authors reported having no funding source or 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.
