Weight Changes From Glucagon-Like Peptide-1 Receptor Agonist Use and Discontinuation: A Retrospective Cohort Study.

Abstract

This study aimed to quantify the effect of glucagon-like peptide-1 receptor agonists (GLP-1s) on weight loss and weight gain following GLP-1 discontinuation. This retrospective cohort study using electronic health records from TriNetX included individuals age 18 years or older with various lengths of continuous GLP-1 use between September 2014 and November 2023. Applying an intention-to-treat framework, we used linear mixed effects models and propensity score adjustment to model changes in BMI after GLP-1 discontinuation while accounting for correlated within-person observations and potential confounders. A total of 78,076 (19.7%) individuals used GLP-1s continuously for 3 months, 23,861 (6.0%) for 6 months, and 12,642 (3.2%) for 9 months. The median BMI prior to initiation was 36.38 (IQR 36.30-36.46), which declined by 2.15% (IQR 2.10%-2.21%) to 35.81 (IQR 35.7-35.92) among individuals with 3 months of continuous GLP-1 use. Median BMI declines were greater among individuals with 6 months (4.38%, IQR 4.27%-4.48%) and 9 months (5.56%, IQR 5.34%-5.78%) of continuous use. On average, weight loss among discontinuers at months 3, 6, and 9 slowed in comparison to their counterparts. Among this real-world sample, GLP-1 use was associated with more modest weight loss than has been demonstrated in randomized controlled trials.