Glucagon-like peptide-1 (GLP-1) receptor agonist therapy duration vs durability of weight loss

Introduction

Despite growing recognition and use for weight loss therapy, there is a need for further investigation into the long-term effects of GLP-1 RA therapy. Objective/Hypothesis: Using a retrospective cohort design, this study sought to ascertain whether there is a duration of therapy with GLP-1 RA after which weight loss is durable. We hypothesized that there would be a duration of therapy after which weight loss is more durable. Methods: We conducted a retrospective study of de-identified electronic health record data to evaluate weight trajectories among adults initiated on semaglutide or tirzepatide between 2005 and 2025. Medication orders were grouped into discrete therapy courses, and weight measurements during treatment and within one year after cessation were linked to each course. The primary outcome was absolute and percent weight change approximately one year after discontinuation, analyzed by treatment duration using descriptive statistics and mixed-effects regression models. Results: Patients treated for <180 days appeared to continue losing weight after discontinuation (−2.35% with semaglutide; −2.85% with tirzepatide), a finding likely attributable to the retrospective design and unverified medication start/stop dates. Subsequent analyses therefore emphasized longer-duration therapy cohorts. Excluding the <180-day group, a trend toward greater weight regain with longer therapy duration was observed, particularly among tirzepatide-treated patients. As such, mixed-effects modeling using all available longitudinal post-treatment weights did not demonstrate a consistent or statistically significant association between longer treatment duration and durability of weight loss; if anything, longer duration trended toward greater regain. Discussion: The study was limited by absent verification of therapy duration owing to study design analyzing medication orders retrospectively. However, subsets of the data were consistent with existing literature and did not identify a duration of therapy that was associated with durable weight loss.