Early Treatment Trajectory and Long‐Term Persistence to Semaglutide for Obesity: A Population‐Based Cohort Study

AIMS: To assess semaglutide persistence in obesity management, identify factors associated with discontinuation and examine early tirzepatide adoption. MATERIALS AND METHODS: This retrospective cohort study used Clalit Health Services records of adults without diabetes initiating Wegovy between January and May 2025. Discontinuation was defined as a gap exceeding 60 days after medication coverage ended. Multivariable Cox models, including a Day-90 landmark analysis, assessed discontinuation. Tirzepatide adoption was evaluated following its December 2025 coverage introduction. RESULTS: Among 34 309 participants (67.0% women; mean age 44.6 years), cumulative discontinuation reached 36.5% at 180 days and 67.6% at 365 days. Arab population sector (hazard ratio [HR] 1.65, 95% CI 1.59-1.72), low socioeconomic status (HR 1.13, 95% CI 1.09-1.17) and current smoking (HR 1.13, 95% CI 1.09-1.17) were associated with discontinuation. In the day-90 landmark cohort (n = 28 218), remaining on 0.25 versus 1.0 mg was associated with subsequent discontinuation (HR 1.88, 95% CI 1.72-2.06), substantially attenuated after adjustment for early refill adherence. Each percentage-point smaller BMI reduction was associated with 3% higher discontinuation hazard (HR 1.03, 95% CI 1.03-1.04). Following tirzepatide availability, 2908 of 33 936 eligible participants (8.6%) initiated treatment over a median 3.1-month observation period. Adoption was associated with higher socioeconomic status and baseline BMI. CONCLUSIONS: Semaglutide discontinuation was common and associated with sociodemographic and early treatment characteristics. Day-90 dose and early weight-loss response may help identify discontinuation risk. Socioeconomic differences suggest inequalities in sustained obesity pharmacotherapy access.