Nearly 65% of patients without type 2 diabetes discontinued glucagon-like peptide-1 receptor agonists within 1 year, a higher rate than those with diabetes, according to a recent study. 

Patricia J. Rodriguez, PhD, MPH, of Truveta Inc in Bellevue, Washington, and her colleagues conducted a retrospective cohort study to examine discontinuation and reinitiation patterns of dual-labeled glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among adult ptients with overweight or obesity. In the study, published in JAMA Network Open, investigators utilized electronic health record data from U.S. health care systems and included 125,474 adult patients who initiated liraglutide, semaglutide, or tirzepatide between January 1, 2018, and December 31, 2023. The patients were stratified by the presence of type 2 diabetes (T2D) and followed for up to 2 years to assess discontinuation and for an additional 2 years to evaluate reinitiation.

Discontinuation, defined as 60 days or more without an active GLP-1 RA prescription, was observed in 46.5% (95% confidence interval [CI] = 46.2%–46.9%) of patients with T2D and 64.8% (95% CI = 64.4%–65.2%) of those without T2D within 1 year. By 2 years, discontinuation rates increased to 64.1% (95% CI = 63.7%–64.5%) and 84.4% (95% CI = 84.0%–84.8%), respectively. Factors significantly associated with discontinuation included moderate to severe gastrointestinal adverse events (T2D: hazard ratio [HR] = 1.38, 95% CI = 1.31–1.45; no T2D: HR = 1.19, 95% CI = 1.12–1.27). Conversely, greater on-treatment weight loss was associated with a lower risk of discontinuation: Each 1% reduction in body weight was associated with a 3.1% (95% CI = 2.9%–3.2%) and 3.3% (95% CI = 3.2%–3.5%) decreased risk of discontinuation among patients with and without T2D, respectively.

Among 81,919 patients who discontinued treatment, 41,792 had available weight data for reinitiation analysis. Within 1 year of discontinuation, 47.3% (95% CI = 46.6%–48.0%) of patients with T2D and 36.3% (95% CI = 35.6%–37.0%) of those without T2D resumed GLP-1 RA therapy. Weight regain was a significant predictor of reinitiation; each 1% increase in weight following discontinuation correlated with a 2.3% (95% CI = 1.9%–2.8%) and 2.8% (95% CI = 2.4%–3.2%) increased risk of reinitiation in patients with and without T2D, respectively.

The findings indicated that while most patients discontinued GLP-1 RAs within 1 year, discontinuation rates were significantly higher and reinitiation rates lower among those without T2D. Discontinuation rates were higher among patients with lower incomes. Extracted clinical notes suggested cost as a contributing factor, though the study’s primary statistical analysis did not focus on direct out-of-pocket affordability.

Full disclosures can be found in the published study.