Weight trajectories after last tirzepatide or semaglutide prescription across a federated health network

Abstract GLP-1 receptor agonist (GLP-1RA) discontinuation has been associated with weight regain. However, weight trajectories following the last documented GLP-1RA prescription in the real-world clinical setting have not been explored. Here, we assessed weight trajectories of 4,182 patients in the six months following their last semaglutide or tirzepatide prescription. Approximately two-thirds of patients showed stable weight or continued weight loss during this period. In a representative subset of 300 patients whose clinical notes were curated using a large language model, treatment discontinuation was documented for 119 patients (40%) around the time of the last prescription. Among these 119 patients, a similar pattern of weight trajectories was observed, with 72% of patients not demonstrating weight regain. Exercise counseling was documented more frequently among patients with durable weight loss after the last GLP1-RA prescription than among those with weight regain (26.2% vs. 14.7%; p = 0.04). Further studies are warranted to evaluate the mechanisms underlying these real-world patterns.