(A-106) Heterogeneity of Treatment Effects of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1) on Weight Loss: A Retrospective Cohort Study

Background: While there is high quality evidence of the effectiveness of GLP-1 receptor agonists (GLP-1) for the treatment of obesity, less is known regarding how such effectiveness may vary across different patient subpopulations.

Objectives: To quantify heterogeneity in weight loss response among GLP-1 users, stratified by patient age, sex, race/ethnicity, diabetes, and baseline body mass index (BMI).

Methods: We used TriNetX, a database containing electronic health records from 81 academic medical centers in the United States, to identify adults with at least 6-month continuous GLP-1 use between September 2014 and November 2023. Our primary outcome was percentage change in BMI from baseline, defined as the most recent BMI measurement within 6 months prior to GLP-1 RA initiation. We used linear mixed-effects models with natural splines to examine BMI changes over time, adjusting for individuals’ demographics and clinical characteristics.

Results: Among 23,291 GLP-1 users, the mean baseline BMI was 37.33 ± 7.71 kg/m² and 65.2% were female. During the 6-month follow-up period, 42% achieved ≥5% BMI reduction. Heterogeneity analyses showed that Older adults (≥65 years) achieved greater weight loss compared to younger patients (-0.40%, 95% CI: -0.60 to -0.20). Female patients had a greater reduction in BMI compared with males (-0.28%, 95% CI: -0.46 to -0.10). Racial differences were also observed. Black patients showed smaller BMI reductions than White patients (0.70%, 95% CI: 0.47 to 0.93). Diabetic patients exhibited a smaller BMI reduction compared to non-diabetic patients (0.76%, 95% CI: 0.53 to 0.99). Compared to patients with baseline BMI < 30, patients with BMI 30-35 had additional -1.72% (95% CI: -1.99 to -1.45) BMI change, and those with BMI≥35 had additional -2.35% (95% CI: -2.60 to -2.11) BMI change.

Conclusions: Among this large, diverse cohort of adults in the United States, real-world effectiveness of GLP-1 was greater among older adults, women, White, those without diabetes, and patients with higher baseline BMI. These findings can be used to inform further research as well as treatment selection among those who may be eligible for pharmacologic treatment of obesity.