Results
We identified 1281 studies through electronic searches, of which 1242 were excluded based on title and abstract. 39 studies were retrieved for detailed assessment, 12 of which were excluded (online supplemental figure 1). 27 RCTs met our inclusion study, providing data for 21 547 participants.8–10 30–53 Table 1 summarises the characteristics of the included trials. These studies were published from 2013 to 2024 and were funded by the pharmaceutical companies Novo Nordisk, Janssen, AstraZeneca, Eli Lilly and Boehringer Ingelheim. The most common incretin-therapy studied was semaglutide (n=12 studies),8 33 37 39–43 45 46 51 52 followed by liraglutide (n=10 studies)30–36 38 43 47 and tirzepatide (n=4 studies).9 44 48 50 The majority of the studies included participants with obesity (BMI ≥30 kg/m2) and/or overweight/obesity (BMI ≥27 kg/m2) with the presence of obesity-related co-morbidities excluding type 2 diabetes. Dedicated RCTs including individuals with type 2 diabetes and BMI ≥27 kg/m2 were also included.31 37 38 44 51 The sample size studied varied between 70 and 3731 participants. These RCTs were performed worldwide and the number of study sites varied from 2 to 191; 2 RCTs were performed in East Asia and included mainly individuals with Asian background.42 52 All included studies had low risk of bias according to RoB 2 (online supplemental table 1).
The meta-analysis of the proportion of individual racial/ethnic groups within the population enrolled in RCTs evaluating GLP-1 medicines for obesity demonstrated a vast predominance of participants self-identified as white/Caucasian. Figure 1 shows the prevalence of each group. Specifically, 26 of the 27 studies included white/Caucasian participants (n=21 146), with a mean prevalence of 79% (95% CI 72% to 85%; I2=99.4%). All studies included non-white participants (n=21 547), with a mean prevalence of 21% (95% CI 15% to 28%; I2=99.3%). Representing the non-white group, the mean prevalence of black/African-American participants was 9% (95% CI 7% to 10%), Asian was 13% (95% CI 1% to 29%) and the proportion of Indigenous participants was 2% (95% CI 1% to 3%) (figure 1). Notably, only 10 studies reported data on Indigenous participants (table 1 and figure 1).9 10 32 40 41 44 48–50 53 18 of the studies included Hispanic/Latino participants, with a mean prevalence of 22% (95% CI 15% to 28%). The funnel plot for prevalence of white-Caucasian and non-white demonstrated no publication bias (Ps>0.10) (data not shown). Regarding biological sex, the majority of the included participants were female (65% (95% CI 60% to 69%; I2=98.3%)).
Next, we completed a meta-analysis of differences in proportions of racial and ethnically diverse peoples between study participants and the general population of the USA, Canada, the UK, Brazil and South Africa (figure 2). We demonstrated that white individuals were well represented in these RCTs as compared with general population of the USA (mean difference +1%, 95% CI −1% to+6%, p=0.19) and the UK (mean difference −2%, 95% CI −5% to+1%, p=0.24) but significantly over-represented as compared with general population of Brazil (mean difference +45%, 95% CI +40% to +50%, p<0.0001) and South Africa (mean difference +547%, 95% CI +524% to +570%, p<0.0001) (figure 2A). Echoing these results, the proportion of non-white individuals accurately represent the prevalence of non-whites in the UK (p=0.91) (figure 2B). However, this racial/ethnic group is significantly under-represented in the RCTs as compared with general population of USA (mean difference −23%, 95% CI −38% to −4%, p=0.002) and Canada (mean difference −34%, 95% CI −47% to −19%, p<0.0001), reaching an alarming gap of −58% (95% CI −66%to −48%, p<0.0001) in relation to Brazil and a striking under-representation of −68% (95% CI −74% to −61%, p<0.0001) as compared with the general population of South Africa (figure 2B).
Addressing each racial and ethnically diverse group individually, we demonstrated that black/African-Americans participants were over-represented in these obesity trials as compared with nations that have reduced proportion of individuals of African descent such as Canada (mean difference +84%, 95% CI +54% to +116%, p<0.0001) and UK (mean difference +94%, 95% CI +64% to +130%, p<0.0001) (figure 2C). On the other hand, black/African-Americans were under-represented in the study population as compared with general population of USA (mean difference −35%, 95% CI −45% to −24%, p<0.0001), Brazil (mean difference −19%, 95% CI −31% to −5%, p=0.011) and South Africa (mean difference −83%, 95% CI −86% to −91%, p<0.0001) (figure 2C). Regarding representation of participants with Asian background, we showed that Asian population was well represented in these RCTs as compared with general population from the USA (p=0.220), Brazil (p=0.695) and South Africa (p=0.068). Conversely, the Asian population was significantly under-represented in relation to Canada (−74%, 95% CI −84% to 56%, p<0.001) and the UK (−50%, 95% CI −70% to −26%, p=0.009) (figure 2D).
The proportion of Indigenous participants in the incretin-based RCTs for obesity was well represented in relation to the USA (p=0.45), but there was a gap of −83% in comparison to prevalence of Indigenous population in Canada (95% CI −97% to −6%, p=0.04) with an even wider discrepancy of −86% in relation to the prevalence of Indigenous population in Brazil (95% CI −97% to −22%, p=0.025) (figure 2E). Regarding the ethnically diverse population of Hispanics/Latinos, the proportion of these groups enrolled in the trials reflects the Hispanic population in the USA (mean difference −16%, 95% CI −39% to +115%, p=0.28) but is over-represented in relation to the proportion of Hispanic/Latinos living in Canada (mean difference +758%, 95% CI +528% to +1007%, p<0.001) (figure 2F).
Further to these analyses, we sought to evaluate the geographical location of study sites worldwide. The 27 RCTs on incretin-based therapies for the treatment of obesity had a total of 1859 study sites located across the globe (table 1). The study sites were distributed predominately in North America (49.3%; USA, Canada, Puerto Rico and Mexico) and Europe (34.3%; Belgium, Bulgaria, Denmark, Germany, France, Finland, Poland, Russia, UK, Hungary, Netherlands, Greece, Spain, Italy, Sweden, Turkey, Czech Republic, Slovakia, Austria, Serbia and Montenegro, Switzerland, Ireland, Norway, Portugal and Ukraine), with the lowest proportion in Australasia (1.1%; Australia and New Zealand), Africa (1.3%; South Africa), South America (5.2%; Brazil and Argentina) and Asia (12.6%; India, Japan, Taiwan, Mainland China and Honk Kong, Israel, United Arab Emirates and South Korea) (figure 3A). Collectively, 84.2% of the study sites were based in high-income countries and only 19.5% in LMIC (figure 3B). These results are in sharp contrast to data on global prevalence of obesity that demonstrates that 66% of adults living with obesity were residing in LMIC in 2020 (ie, only 34% in high-income countries) (figure 3C). Moreover, the projected estimates of obesity for 2025 and 2035 are dominant in LMIC as compared with its prevalence in high-income countries (figure 3C). As demonstrated in figure 4, while the global prevalence of overweight/obesity (WHO) is greatest in North America, South America, Australasia, North Africa (Morocco, Algeria, Libya, Egypt) and countries in Western Asia (Saudi Arabia, Iraq and Iran), the greatest prevalence of study sites in this meta-analysis was in the USA (40.5%), with other countries being vastly under-represented.