Women lost a larger average share of their starting body weight than men in randomized trials of GLP-1 receptor agonists, according to a systematic review and meta-analysis reported in JAMA Internal Medicine. Researchers cautioned that the result identifies a pattern across trials rather than explaining why that difference occurred.
Six trials involving nearly 20,000 participants reported weight outcomes by sex. Across those studies, women lost an average 10.88% of baseline body weight while men lost 6.8%. The researchers found that treatment effects were otherwise generally consistent in analyses grouped by race, ethnicity, age, starting body-mass index and HbA1c, a measure used to assess blood-sugar control.
The broader review covered 41 articles representing 64 randomized clinical trials. Follow-up periods ranged from 12 to 144 weeks, and nearly all of the trials were funded by industry. Investigators searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials for research published through July 2024.
Most of the 48 trials that could be characterized individually studied semaglutide. The review also covered dulaglutide, liraglutide, exenatide and combination products pairing insulin with a GLP-1 medicine. Tirzepatide was excluded because it acts on both GIP and GLP-1 receptors, making it different from the medicines selected for the analysis.
Subgroup reporting was uneven. Three-quarters of the characterized trials assessed differences by baseline BMI, half examined HbA1c and about 44% examined age. Only about one-fifth assessed outcomes by sex. That limited reporting means the apparent difference between women and men rests on a smaller subset of the available randomized evidence, even though the number of participants in those studies was substantial.
The analysis was not designed to establish a biological mechanism. Researchers raised several possibilities for future study, including interactions with estrogen, differences in drug processing, body composition and lower median body weight among women. Those explanations remain hypotheses and should not be treated as established reasons for the finding.
The result may help clinicians frame discussions about the range of outcomes seen in trials, but it does not provide a basis for changing an individual's medicine without medical advice. Effectiveness is only one part of treatment decisions, which also involve side effects, approved indications, other health conditions, access and cost.
The authors called for more studies that can reliably compare patient groups, particularly people who have historically been underrepresented in trials. With GLP-1 medicines widely used and expensive, better subgroup evidence could clarify who benefits, by how much, and under what circumstances.
