(A-086) Weight Changes from Glucagon-Like Peptide-1 Receptor Agonist (GLP-1) Use and Discontinuation: A Retrospective Cohort Study of Electronic Health Records

Background: Despite a surge of interest in glucagon-like peptide-1 agonists (GLP-1s) for the treatment of obesity, the real-world effect of GLP-1s on weight has not been well characterized, nor is it clear how much weight is regained upon treatment discontinuation.

Objectives: To quantify the effect of GLP-1s on weight loss, and weight gain following GLP-1 discontinuation.

Methods: In this retrospective cohort study, we used electronic health records from TriNetX, a proprietary database containing longitudinal patient information derived from approximately 70 academic medical centers in the United States. We included individuals age 18 years or older with various lengths of continuous GLP-1 use (3, 6 and 9 months) between September 2014 and November 2023, at least one baseline BMI, and at least two BMIs following GLP-1 initiation. The main outcome was change in body mass index from baseline. We compared the effect of continued vs. discontinued GLP-1 medications among individuals who consecutively took the medications for 3, 6, and 9 months using longitudinal structural mixed model. We applied intention-to-treat framework, and used linear mixed effects models and propensity score adjustment to model changes in body mass index (BMI) after GLP-1 discontinuation while accounting for correlated within-person observations and potential confounders.

Results: The final cohort contained 395,973 individuals, of whom 78,751 (19.9%) used GLP-1s continuously for three months, 24,024 (6.1%) for 6 months and 12,685 (3.2%) for 9 months. The median (interquartile range [IQR]) BMI prior to initiation was 36.38 (36.31-36.45), which declined by 2.15% (95% confidence intervals [CI] 2.10-2.21) to 35.81, IQR 35.7-35.92 among individuals with three months of continuous GLP-1 use. Median BMI declines were greater among individuals with 6 months (4.38%, CI 4.27-4.48%) and 9 months (5.56%, CI 5.34-5.78%) of continuous use. Many discontinuers at a given month reinitiated GLP-1s subsequently. On average, weight loss among discontinuers at months 3, 6 and 9 using this intention-to-treat framework slowed in comparison to their counterparts, though remained below average weight prior to initiating GLP-1 treatment. For example, among individuals with three months of continuous GLP-1 use, individuals who discontinued on month 4 had 3.7% reduction in BMI vs. 4.5 % among those who continued.

Conclusions: Among this real-world sample, GLP-1 use was associated with more modest weight loss than has been demonstrated in randomized controlled trials. Discontinuation and reinitiation of treatment was common.