A study conducted using electronic health record data from a collective of U.S. healthcare systems found that most adults with overweight or obesity discontinued glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy within one year. Discontinuation rates were significantly higher and reinitiation rates were significantly lower for patients without type 2 diabetes.

GLP-1 RAs are used for weight management and glycemic control, with evidence suggesting that continued use is necessary for sustained benefits. Concerns related to cost, tolerability, and access may be contributing to high discontinuation rates. Previous studies have reported widely varying discontinuation rates, but data on reinitiation patterns remain limited.

In the study, "Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity," published in JAMA Network Open, researchers investigated the rates at which people stopped using the popular weight loss drugs.

A retrospective cohort analysis included 125,474 adults with overweight or obesity who initiated treatment with liraglutide, semaglutide, or tirzepatide between January 1, 2018, and December 31, 2023. Eligible patients had a body mass index of 27 or higher, a weight measurement within 60 days before initiation, and regular health care interactions in the previous year.

Discontinuation was defined as 60 days without any GLP-1 RA on hand. Reinitiation was defined as the first fill of any GLP-1 RA after discontinuation. Patients were followed for up to two years for discontinuation and two additional years for reinitiation. Time-to-event outcomes were assessed using Kaplan-Meier models and Cox proportional hazards regression.

Within one year, 46.5% of patients with type 2 diabetes and 64.8% without type 2 diabetes discontinued GLP-1 RA therapy. Within two years, discontinuation rates increased to 64.1% and 84.4%, respectively. Gastrointestinal adverse events were linked to the discontinuation rates.

Among 41,792 patients who discontinued and had a weight measurement at discontinuation, 47.3% of patients with type 2 diabetes and 36.3% without type 2 diabetes reinitiated therapy within one year. Weight regain was significantly associated with reinitiation, with a 1% weight gain increasing the hazard by 2.3% for patients with type 2 diabetes and 2.8% for those without. Patients aged 65 years or older were less likely to reinitiate treatment.

GLP-1 RA discontinuation rates were high, particularly for patients without type 2 diabetes, who also had lower reinitiation rates. Weight loss during treatment was associated with lower discontinuation, while weight regain after discontinuation was linked to higher reinitiation.

More information: Patricia J. Rodriguez et al, Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity, JAMA Network Open (2025). DOI: 10.1001/jamanetworkopen.2024.57349

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