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

This real-world observational study examined weight trajectories in 4,182 patients during the 6 months following their last documented semaglutide or tirzepatide prescription, drawn from a federated health network. The study found that approximately two-thirds of the full cohort showed stable weight or continued weight loss after their final prescription. In a representative subset of 300 patients whose clinical notes were analyzed using a large language model (LLM), treatment discontinuation was confirmed in 119 patients (40%), and of those, 72% did not demonstrate weight regain. The study also noted that exercise counseling was documented more frequently among patients who maintained weight loss compared to those who experienced weight regain (26.2% vs. 14.7%; P = .04). Key limitations include the observational and retrospective design, reliance on documented prescriptions rather than confirmed medication use, potential incompleteness of clinical records, use of an LLM for data curation introducing possible inaccuracies, and the inability to establish causation. The authors acknowledge that further studies are needed to understand the mechanisms behind these real-world patterns of weight maintenance after GLP-1 receptor agonist discontinuation.

Why this grade: While the study includes a substantial human cohort (n=4,182), its retrospective observational design, reliance on prescription records rather than confirmed adherence, and lack of a control group limit the strength of causal inference.