GLP-1 Drugs May Work Differently in Women

# GLP-1 Drugs May Work Differently in Women **Key Takeaways:** - A meta-analysis found that women lost more weight than men while taking a GLP-1 receptor agonist. - Biological differences, such as estrogen levels and body composition, may explain why women respond more to these agents. - Weight loss was consistent across many other patient subgroups broken down by age, race and ethnicity, body mass index, and HbA1c. Women lost more weight than men while using GLP-1 receptor agonists, according to a systematic review and meta-analysis of randomized clinical trials. Among six trials that analyzed outcomes for nearly 20,000 participants by sex, women lost an average of 10.88% (95% CI -14.76 to -7) of their baseline body weight on a GLP-1 agent, while men lost 6.8% (95% CI -4.6 to -9), as reported by G. Caleb Alexander, MD, MS, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, and co-authors. The weight-loss effects of GLP-1 agents were generally consistent across other subgroups, including those stratified by race, ethnicity, age, baseline body mass index (BMI), and HbA1c. The researchers noted, "Although our synthesis suggests that GLP-1 receptor agonists produce greater weight loss among women than men, their efficacy was consistent across many other important subpopulations of patients who may be eligible for treatment." Co-author Hemalkumar Mehta, PhD, MS, also of Johns Hopkins, acknowledged the high demand for these costly medications. He stated, "We need more studies like this to better understand the benefits of these products in clinical practice, especially for individuals that might be under-represented in clinical trials." Previous data have suggested that certain patient groups, including men, may not reap as much weight-loss benefit, prompting the research team to explore whether specific patient factors influenced these outcomes. Mehta expressed surprise at the findings, saying, "This prompted us to look closely at biological and mechanistic reasons -- how hormones and body composition might play a role." He mentioned potential factors influencing the greater weight loss among women, including interactions with estrogen, how women’s bodies process the drug, and women's lower median body weight. Mehta noted that the study wasn’t designed to quantify differences in the length of drug use, but indicated that men and women likely used the drugs for similar durations based on the nature of randomized clinical trials. To assess treatment effects across GLP-1 agents, Alexander's team analyzed articles from MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials published through July 2024. The meta-analysis included 41 articles representing 64 randomized clinical trials, many of which were industry-funded. Of 48 trials characterized, most focused on semaglutide (Ozempic, Wegovy), with others including dulaglutide (Trulicity), liraglutide (Victoza, Saxenda), and exenatide (Byetta, Bydureon BCise). While all are indicated for type 2 diabetes, only semaglutide and liraglutide have specific indications for weight loss. Across the trials, heterogeneity of treatment effects was most commonly assessed using baseline BMI (75%), HbA1c (50%), and age (43.8%), less commonly by ethnicity (25%), race (22.9%), or sex (20.8%). Notably, tirzepatide (Mounjaro, Zepbound), which has emerged as the most effective weight-loss drug containing a GLP-1 agent, was excluded from this analysis because it is a dual GIP and GLP-1 receptor agonist.