Discontinuation and Reinitiation of GLP-1 Receptor Agonists Among US Adults with Overweight or Obesity

ImportanceAdherence to GLP-1 RA is important for efficacy. Discontinuation and reinitiation patterns for patients with and without type 2 diabetes (T2D) are not well-understood. ObjectiveTo describe rates and factors associated with discontinuation and reinitiation of GLP-1 RA, for patients with and without T2D. DesignIn this retrospective cohort study, adults with overweight or obesity initiated on GLP-1 RA between January 2018 and December 2023 were identified using electronic health record (EHR) data from a collective of 30 US healthcare systems. Patients were followed for up to 2 years to assess discontinuation and for 2 additional years to assess reinitiation. SettingClinical and prescribing data from EHRs linked to dispensing information ParticipantsAdults newly initiated on GLP-1 RA between 2018 and 2023, with a baseline BMI [≥]27 and an available weight measurement within 60 days before initiation, and regular care in the year before initiation. Exposure/CovariatesPatients were stratified by presence of T2D at baseline. Associations with socio-demographics, health factors, weight changes, and gastrointestinal (GI) adverse events (AE) were modeled. Main Outcomes and MeasuresProportion of patients discontinuing and reinitiating GLP-1 RA were estimated from Kaplan-Meier models. Associations between covariates and discontinuation and reinitiation outcomes were modeled using time-varying Cox proportional hazards models. All analyses were conducted for patients with and without T2D. ResultsAmong 96,544 adults initiating GLP-1 RA, the mean (SD) age was 55.1 (13.3) years, 65.2% were female, 73.7% were white, and 61.3% had T2D. Individual income exceeded $50,000 for 49.7% of patients with and 57.2% of patients without T2D. One-year discontinuation was significantly higher for patients without T2D (65.1%), compared to those with T2D (45.8%). Higher weight loss, absence of GI AE, and higher income (T2D only) were significantly associated with higher discontinuation. Of 28,142 who discontinued and had a discontinuation weight available, one-year reinitiation was lower for those without T2D (34.7%), compared to those with T2D (51.0%). Weight re-gain was significantly associated with increased reinitiation. Conclusions and RelevanceMost patients with overweight or obesity discontinue GLP-1 RA within 1 year, but those without T2D discontinue at higher rates and reinitiate at lower rates. Inequities in access and adherence to effective treatments have the potential exacerbate disparities in obesity. Key pointsO_ST_ABSQuestionC_ST_ABSHow frequently do adults with overweight or obesity discontinue and subsequently reinitiate GLP-1 RA? What factors are associated with these outcomes? FindingsIn this study of 96,544 patients initiating GLP-1 RA, 46% of patients with and 65% without type 2 diabetes (T2D) discontinued within 1 year. Weight loss, income, gastrointestinal adverse events, and comorbidities were significantly associated with discontinuation. Following discontinuation, 51% of patients with and 35% without T2D reinitiated within a year. Weight re-gain since discontinuation was significantly associated with reinitiation. MeaningWhile most patients discontinue GLP-1 RA within a year, discontinuation is significantly higher and reinitiation is significantly lower for patients without T2D. Weight changes, tolerability, and proxies of access to care are significantly associated with sustained treatment.