Discontinuation and Reinitiation of GLP-1 Receptor Agonists Among US Adults with Overweight or Obesity
Authors: Rodriguez Patricia J. , Zhang Vincent , Gratzl Samuel , Do Duy , Cartwright Brianna Goodwin , Baker Charlotte , Gluckman Ty J. , Stucky Nicholas , Emanuel Ezekiel J. 
Published: July 2024

AbstractImportanceAdherence 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 informationParticipantsAdults 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 pointsQuestionHow 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.