Treatment Gaps: GLP-1 RA Discontinuation Higher in Patients Without Type 2 Diabetes, Study Finds

"Individuals without type 2 diabetes were more likely to discontinue GLP-1 receptor agonist therapy compared to those with the condition. Moreover, they exhibited lower rates of reinitiation, suggesting potential barriers to sustained treatment," the researchers wrote in JAMA Network Open. "These disparities raise concerns about adherence to effective weight management therapies and their long-term impact on health outcomes."

While GLP-1 receptor agonists effectively promote weight reduction and metabolic improvements, their long-term success depends on consistent use. However, adherence remains challenging, and discontinuation and reinitiation patterns are poorly understood. To enhance patient adherence, healthcare providers may need to implement strategies such as better education on the benefits of sustained therapy, proactive management of side effects, and personalized treatment plans.

Against the above background, Patricia J. Rodriguez, Truveta Inc, Bellevue, Washington, and colleagues aimed to examine the rates and determinants of discontinuation and subsequent reinitiation of GLP-1 RAs in adults with overweight or obesity.

For this purpose, the researchers conducted a retrospective cohort study including 125,474 adults with overweight or obese who newly initiated treatment with a dual-labeled GLP-1 receptor agonist—liraglutide, semaglutide, or tirzepatide—between January 1, 2018, and December 31, 2023. Participants had a baseline body mass index of 27 or more, a recorded weight measurement within 60 days before initiation, and regular care in the prior year. Follow-up lasted up to two years for discontinuation assessment and an additional two years for reinitiation.

Patients were stratified by type 2 diabetes status. Discontinuation and reinitiation rates were estimated using Kaplan-Meier models. The sociodemographic factors, health conditions, weight changes, and gastrointestinal adverse events were analyzed using time-varying Cox proportional hazards regression models. Analyses were conducted separately for patients with and without type 2 diabetes.

Key Findings:

• The study included 125,474 adults with a mean age of 54.4 years, of whom 65.4% were women. Among the participants, 61.0% had type 2 diabetes.
• One-year discontinuation rates were higher for patients without type 2 diabetes (64.8%) than those with type 2 diabetes (46.5%).
• Greater weight loss was linked to lower discontinuation rates, with a 1% reduction in weight lowering the hazard of discontinuation by 3.1% in patients with type 2 diabetes and 3.3% in those without.
• Higher-income (>$80,000) was associated with a lower risk of discontinuation in patients with type 2 diabetes (HR: 0.72).
• Moderate or severe gastrointestinal adverse events increased the risk of discontinuation (HR: 1.38 for patients with type 2 diabetes and 1.19 for those without).
• Among 41,792 patients with available weight data at discontinuation, one-year reinitiation rates were lower for those without type 2 diabetes (36.3%) than those with type 2 diabetes (47.3%).
• Weight regain of 1% after discontinuation was associated with an increased likelihood of reinitiation, with a 2.3% higher hazard in patients with type 2 diabetes and 2.8% in those without.

The study found that most adults with overweight or obesity discontinued GLP-1 RA therapy within a year, with significantly higher discontinuation and lower reinitiation rates among those without type 2 diabetes. Greater weight loss and higher income (in patients with type 2 diabetes) were linked to lower discontinuation, whereas weight regain after discontinuation was associated with a higher likelihood of reinitiation.

"Differences in access and insurance coverage for patients without type 2 diabetes may have contributed to these patterns. Inequities in access and adherence to effective treatments could further widen existing disparities in obesity management," the researchers concluded.

Reference:

Rodriguez PJ, Zhang V, Gratzl S, et al. Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity. JAMA Netw Open. 2025;8(1):e2457349. doi:10.1001/jamanetworkopen.2024.57349