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, the real-world association between discontinuation of GLP-1RA prescriptions and weight change has not been explored. We assessed weight trajectories of 4,182 patients in the six months following their last GLP-1RA prescription. Approximately two-thirds of patients showed stable weight or continued weight loss during this period post the last known GLP-1RA prescription. In a representative subset of patients with clinician-documented discontinuation near the last prescription (N=300), a similar distribution of weight regain in a minority of patients was observed vs no regain in the majority of patients during the six-month post-GLP-1RA prescription period. To mirror clinical trial-style discontinuation definitions, we also evaluated cohorts with no subsequent GLP-1RA prescription for 1 year after the last prescription (semaglutide N=1,755; tirzepatide N=1,312), observing weight regain in a minority of patients (39.3% semaglutide; 26.6% tirzepatide) and no weight regain in the majority (60.7% semaglutide; 73.4% tirzepatide) in the year following the last known GLP-1RA prescription. Exercise counseling was documented more frequently among patients with durable weight loss post-last GLP1 prescription compared with those with weight regain (26.2% vs. 14.7%; p=0.04). Further studies are warranted to infer the mechanisms underlying these real-world patterns.