(A-104) Heterogeneity of treatment effects of glucagon-like peptide-1 receptor agonists (GLP-1 RA's) for weight loss among adults: A systematic review and meta-analysis of randomized trials

Background: It is unclear whether and how much the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) varies based on individuals’ sociodemographic and clinical characteristics.

Objectives: To quantify evidence of heterogeneity of treatment effects in randomized controlled trials (RCTs) of GLP-1 RA’s (semaglutide, liraglutide, tirzepatide, exenatide, lixisenatide, and dulaglutide) with respect to age, sex, race, ethnicity, and baseline body mass index (BMI).

Methods: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify RCTs of GLP-1 RAs from database inception through July 26, 2024. We included studies that described single RCTs, multiple RCTs with pooled results, and multiple RCTs with separately reported results. Pairs of investigators independently screened titles/abstracts and full texts. From each eligible study, we extracted the study design, intervention, comparators, baseline characteristics, and weight change over time (our key outcome), overall and stratified by subgroups of interest. We meta-analyzed mean changes in weight and 95% confidence intervals (CIs) using random-effect models.

Results: Our searches identified 11,962 records. We included 44 studies representing 61 different RCTs. Among the 44 studies, 5 studies pooled multiple RCTs together, and 12 studies included multiple RCTs and reported results separately by each RCT. Most studies stratified weight loss analyses by baseline BMI (29 studies, 54 RCTs), and some studies did so by sex (9 studies, 10 RCTs). Based on preliminary synthesis of 9 studies representing 11 RCTs, weight loss was comparable between individuals aged ≥65 years (-2.01 kg; 95% CI: -3.19, -0.84) and those < 65 years (-2.05 kg; 95% CI: -3.03, -1.07), while females (-11.24%, 95% CI: -16.22%, -6.26%) achieved greater weight loss than males (-7.64%, 95% CI: -11.58%, -3.70%).

Conclusions: Our preliminary results indicated that the effectiveness of GLP-1 RAs was similar across age groups but greater among females than males. Future synthesis that includes all RCTs and subgroups (which will be completed before the conference) will provide fundamental new knowledge regarding the heterogeneity of treatment effects of GLP-1 RAs, which will be useful for clinical care and scientific investigation alike.