Demographic Disparities in GLP-1 RA Trial Enrollment Raise Inclusivity, Validity Concerns

New research is shedding light on notable demographic and regional disparities in access to GLP-1 receptor agonist (RA) clinical trials for weight loss, raising concerns about the external validity of such trials.1

The data were presented at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting by Kimberly Ho, MD, Brown University, and highlight substantial underrepresentation of Black, Hispanic, and American Indians/Natives in GLP-1 RA RCTs, especially in the US despite bearing a greater obesity burden.1

In 2005, exenatide (Byetta) became the first GLP-1 RA to receive approval from the US Food and Drug Administration. Since then, the class has exploded in popularity, with multiple agents receiving subsequent indications across type 2 diabetes, overweight and obesity, cardiovascular disease, kidney disease, and most recently, liver disease.1,2

“We suspect that GLP-1 RA trial generalizability may be limited by relative underrepresentation of key affected patient populations,” Ho and colleagues wrote.1

To assess demographic and regional representation in GLP-1 RA weight loss RCTs, investigators conducted a meta-analysis of 149 English-language RCTs assessing GLP-1 RAs for weight loss from 2015 to 2025.1

A total of 61 RCTs involving 59,425 participants met inclusion criteria for meta-analysis (45 US, 16 international). The mean age of trial participants was 54.7±6.7 years and most were female (95% CI, 46–54%; I² = 98.8%). Most individuals were White (69% overall; I² = 99.91%), including 75% in US RCTs and 47% in international RCTs.1

Investigators noted US RCTs were 4 times more likely to include White participants (risk ratio [RR], 4.10; 95% CI, 4.05-4.16). Hispanic or Latino participants made up 24% (I² = 99.84%), with 27% in the US versus 11% internationally (RR, 1.93; 95% CI, 1.85–2.01). Black participants comprised 6% of all participants (I² = 99.14%), with 6% in the US and 7% internationally. Investigators pointed out US RCTs were 15% less likely to include Blacks (RR, 0.85; 95% CI, 0.74-0.97).1

Further analysis revealed 19% of participants were Asian (I² = 99.97%), with 11% in the US and 42% internationally. Of note, RCTs conducted internationally were 7 times more likely to include Asians than those conducted in the US (RR, 6.92; 95% CI, 6.86-6.98).1

Additionally, American Indians/Natives accounted for 2% of trial participants (I² = 99.91%), with 3% in the US and 1% internationally. Upon analysis, RCTs conducted in the US were 15% more likely to include American Indians/Natives (RR, 1.15; 95% CI, 0.94-1.36).1

Relative to the overall prevalence of obesity in the US, investigators noted Black (6% in this meta-analysis vs 20% of US obesity), Hispanic (27% vs 31%), and American Indian/Native (3% vs 19%) patients were underrepresented in GLP-1 RA trials for weight loss. However, non-Hispanic White (75% in this meta-analysis vs 17% of US obesity) patients were overrepresented in the present analysis, and Asian Americans were properly represented.1

“These disparities raise critical concerns about the external validity of GLP-1 RCTs,” investigators concluded.1 “Inclusive and representative trial enrollment is essential to address existing health disparities across global populations and advance health equity.”

References

1. Ho K, Das TS, Monteiro J, et al. Demographic and Regional Disparities in GLP-1 Receptor Agonist Clinical Trials for Weight Loss: A Comparative Meta-Analysis of US and International RCTs. Presented at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting. Phoenix, Arizona. October 27-29, 2025.

2. Brooks A. FDA Approves Semaglutide (Wegovy) Injection 2.4 mg for Noncirrhotic MASH. HCPLive. August 15, 2025. Accessed October 27, 2025. https://www.hcplive.com/view/fda-approves-semaglutide-wegovy-injection-2-4-mg-for-noncirrhotic-mash