OBJECTIVE: The objective of this study was to characterize changes in body weight and glycated hemoglobin (in those with prediabetes at baseline) through 12 months by obesity pharmacotherapy discontinuation status. METHODS: This retrospective cohort study used electronic health record data from a large health system in Ohio and Florida to identify adults with overweight or obesity without type 2 diabetes who initiated injectable semaglutide or tirzepatide between 2021 and 2023. Treatment discontinuation was defined by a >90-day gap between exhaustion of previous supply and next dispense or end of study follow-up (December 2024) and was classified into early discontinuation (i.e., within 3 months of index date) and late discontinuation (i.e., within 3-12 months). RESULTS: We identified 7881 patients; 6109 received semaglutide, and 1772 received tirzepatide. A total of 80.8% had low maintenance dosages. Mean (SD) percentage weight reduction at 1 year was 8.7% (9.6%); and it was 3.6% (8.1%) with early discontinuation, 6.8% (9.1%) with late discontinuation, and 11.9% (9.2%) with non-discontinuation (p < 0.001). The mean (SD) absolute reduction in percent glycated hemoglobin at 1 year was 0.1 (0.4) with early discontinuation, 0.2 (0.4) with late discontinuation, and 0.4 (0.4) with non-discontinuation (p < 0.001). CONCLUSIONS: The average weight reduction in this cohort was lower than that observed in the main phase 3 trials, likely because of higher rates of discontinuation and lower maintenance dosages.