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. 2025 Jan 2;8(1):e2457349.
doi: 10.1001/jamanetworkopen.2024.57349.

Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity

Patricia J Rodriguez  1 , Vincent Zhang  2 , Samuel Gratzl  1 , Duy Do  1 , Brianna Goodwin Cartwright  1 , Charlotte Baker  1 , Ty J Gluckman  3 , Nicholas Stucky  1 , Ezekiel J Emanuel  2
Affiliations

Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity

Patricia J Rodriguez et al. JAMA Netw Open. .

Abstract

Importance: Adherence to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is important for their effectiveness. Discontinuation and reinitiation patterns are not well understood.

Objective: To describe rates of and factors associated with discontinuation and subsequent reinitiation of GLP-1 RAs among adults with overweight or obesity.

Design, setting, and participants: In this retrospective cohort study, 125 474 adults with overweight or obesity newly initiated treatment with a dual-labeled GLP-1 RA (liraglutide, semaglutide, or tirzepatide) between January 1, 2018, and December 31, 2023, with a baseline body mass index of 27 or more, an available weight measurement within 60 days before initiation, and regular care in the year before initiation were identified using electronic health record data from a collective of US health care systems. Patients were followed up for up to 2 years to assess discontinuation and for 2 additional years to assess reinitiation.

Exposure: Patients were stratified by presence of type 2 diabetes at baseline.

Main outcomes and measures: Proportions of patients discontinuing and reinitiating GLP-1 RA were estimated from Kaplan-Meier models. Associations of sociodemographic characteristics, health factors, weight changes, and gastrointestinal adverse events with discontinuation and reinitiation outcomes were modeled using time-varying Cox proportional hazards regression models. All analyses were conducted separately for patients with and patients without type 2 diabetes.

Results: In this cohort study of 125 474 adults (mean [SD] age, 54.4 [13.1] years; 82 063 women [65.4%]), 76 524 (61.0%) had type 2 diabetes. One-year discontinuation was significantly higher for patients without type 2 diabetes (64.8% [95% CI, 64.4%-65.2%]) compared with those with type 2 diabetes (46.5% [95% CI, 46.2%-46.9%]). Higher weight loss (1% reduction in weight from baseline was associated with a 3.1% [95% CI, 2.9%-3.2%] lower hazard of discontinuation for patients with type 2 diabetes and a 3.3% [95% CI, 3.2%-3.5%] lower hazard of discontinuation for patients without type 2 diabetes) and higher income (type 2 diabetes only; >$80 000: hazard ratio [HR], 0.72 [95% CI, 0.69-0.76]) were significantly associated with lower rates of discontinuation, while moderate or severe incident gastrointestinal adverse events were associated with a higher hazard of discontinuation (with type 2 diabetes: HR, 1.38 [95% CI, 1.31-1.45]; without type 2 diabetes: HR, 1.19 [95% CI, 1.12-1.27]). Of 41 792 patients who discontinued and had a discontinuation weight measurement available, 1-year reinitiation was lower for those without type 2 diabetes (36.3% [95% CI, 35.6%-37.0%]) compared with those with type 2 diabetes (47.3% [95% CI, 46.6%-48.0%]). Weight regain of 1% from discontinuation was significantly associated with increased hazards of reinitiation of 2.3% (95% CI, 1.9%-2.8%) for patients with type 2 diabetes and 2.8% (95% CI, 2.4%-3.2%) for patients without type 2 diabetes.

Conclusions and relevance: In this cohort study, most patients with overweight or obesity discontinued GLP-1 RA therapy within 1 year, but those without type 2 diabetes had higher discontinuation rates and lower reinitiation rates. Inequities in access and adherence to effective treatments have the potential to exacerbate disparities in obesity.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Emanuel reported receiving personal fees from the University of California San Francisco, Advocate Aurora Health, Cain Brothers, Bowdoin College, The Suntory Foundation, Ontario Hospital Association, University of Oklahoma, Sanford Health, Health Plan Alliance, Emory Health Care, and Employer Direct Health Care; nonfinancial support from Galien Foundation, Hlth Inc, National University of Singapore, Hawaii Medical Services Association, Tel Aviv University, The Quadrangle, Lazard, University of Bergen, University of Virginia, New York Historical Society, Amangiri, Forerunner Conference, BCEPS International Symposium, Future of Science, Cell and Gene Therapy, and Arendalsuka Meeting during the conduct of the study; and serving as a member of the Board of Advisors for Cellares Corp, advisor for Clarify Health Solutions, advisor for Notable Health, member of the Advisory Board for JSL Health, member of the Advisory Board for Peterson Center of Healthcare, special advisor to the Director General of the World Health Organization (WHO), member of the Expert Advisory Group WHO COVID-19 committee, member of the Advisory Board of the HIEx Health Innovation Exchange Partnership sponsored by the United Nations, member of the WHO Expert Group on Ethics & Governance of Outbreaks/Emergencies, member of the WHO Guideline Development Group on the Use and Indications of GLP-1s for Adults Living With Obesity, member of the Internal Advisory Board of The Penn Parity Center, advisor for Link Health Technologies, advisor for Nuna Health, member of the Board of Advisors of Alto Pharmacy, consultant for Korro/Coach AI, consultant for Aberdeen Inc, member of the Advisory Board of FeelBetter Inc, member of the Advisory Board of Biden’s Transition COVID-19 Committee, and member of the JAMA Editorial Board. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Proportions Discontinuing and Reinitiating Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Within 2 Years
Discontinuation is the first date a patient is 60 days or more without any GLP-1 RA medication on hand. Reinitiation is the first fill of any GLP-1 RA after discontinuation. Patients were censored at their last encounter before November 5, 2024, or administrative censoring (2 years), whichever occurred first. The y-axis represents the event probability (1-survival probability).
Figure 2.
Figure 2.. Associations Between Covariates and Discontinuation Outcomes for Patients With or Without Type 2 Diabetes
Points represent hazard ratios (HRs) from separate Cox proportional hazards regression models for patients with or without type 2 diabetes, plotted on a log scale. Lines represent 95% CIs, plotted on a log scale. Tabular HRs (95% CIs) are provided on an exponentiated (HR) scale. The comparator reference level for sex was female, for race and ethnicity was White, and for income was $30 000 or less. Baseline hazards were stratified by initiation year. BMI indicates body mass index; CKD, chronic kidney disease. aIncludes Alaska Native or American Indian, Hawaiian or Pacific Islander, multiple races, other single races, and unknown or missing race.
Figure 3.
Figure 3.. Associations Between Covariates and Reinitiation Outcomes for Patients With or Without Type 2 Diabetes
Points represent hazard ratios (HRs) from separate Cox proportional hazards regression models for patients with or without type 2 diabetes, plotted on a log scale. Lines represent 95% CIs, plotted on a log scale. Tabular HRs (95% CIs) are provided on an exponentiated (HR) scale. The comparator reference level for sex was female, for race and ethnicity was White, and for income was $30 000 or less. Baseline hazards were stratified by initiation year. BMI indicates body mass index; CKD, chronic kidney disease. aIncludes Alaska Native or American Indian, Hawaiian or Pacific Islander, multiple races, other single races, and unknown or missing race.
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