S2461 Demographic and Regional Disparities in GLP-1 Receptor Agonist Clinical Trials for Weight Loss: A Comparative Meta-Analysis of US and International RCTs

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) treat obesity, which disproportionately affects racial/ethnic minorities, including 20% of Black adults, 18% Hispanic, and 19% American Native/Indian compared to 16% White adults and 7% Asian Americans in the U.S. (NIH). We conducted a meta-analysis (MA) to assess demographic and regional representation in GLP-1 RA weight-loss randomized controlled trials (RCTs) because we suspect that GLP-1 RA trial generalizability may be limited by relative underrepresentation of key affected patient populations. Methods: We reviewed 149 English-language RCTs that looked at GLP-1 RAs for weight loss from 2015 to 2025. Random-effects MA assessed demographic and clinical differences in US vs international trials using RRs. Results: Sixty-one RCTs met inclusion criteria for MA (n = 59,425, 45 US, 16 international). Mean age was 54.7 ± 6.7 years and most were woman (95% CI: 46–54%, I² = 98.8%). Whites comprised 69% overall (I² = 99.91%), including 75% in U.S. RCTs and 47% in international RCTs. US RCTs were 4 times more likely to include Whites (4.10 [4.05-4.16]). Hispanic or Latinos made up 24% (I² = 99.84%), with 27% in U.S. vs 11% internationally (RR 1.93 [1.85–2.01]). Blacks were 6% overall (I² = 99.14%), with 6% in US and 7% internationally. US RCTs were 15% less likely to include Blacks (RR 0.85 [0.74-0.97]). Overall, 19% were Asian (I² = 99.97%), with 11% in the US and 42% internationally. RCTs conducted internationally were 7 times more likely to include Asians than those conducted in the U.S. (RR 6.92 [6.86-6.98]). American Indians/Natives (AI/AN) accounted for 2% (I² = 99.91%), with 3% in the US and 1% internationally. RCTs conducted in the U.S. were 15% more likely to include AI/AN (1.15 [0.94-1.36]). Blacks (6% in this MA vs 20% of U.S. obesity), Hispanic (27% vs 31%), and AI/AN (3% vs 19%) patients were more underrepresented than the overall U.S. obesity prevalence (NIH). Non-Hispanic Whites (75% in this MA vs 17% of U.S. obesity) were overrepresented in our study. Asian Americans were properly represented. Conclusion: These findings reveal substantial underrepresentation of Black, Hispanic, and AI/AN in GLP-1 RA RCTs, especially in the U.S. despite bearing a higher obesity burden. These disparities raise critical concerns about the external validity of GLP-1 RCTs. Inclusive and representative trial enrollment is essential to address existing health disparities across global populations and advance health equity.