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.