High discontinuation rates of GLP-1 agonists found among patients with obesity

By Dr. Priyom Bose, Ph.D.Reviewed by Danielle Ellis, B.Sc.Feb 4 2025

Nearly half of patients with type 2 diabetes and two-thirds without discontinue GLP-1 receptor agonists within a year, with weight loss, income, and adverse events influencing discontinuation and weight regain driving reinitiation

A recent JAMA Network Open study investigated the factors associated with discontinuation and subsequent reinitiation of GLP-1 RAs among overweight or obese adults residing in the US.

Weight-related health conditions and the use of GLP-1 RAs

Almost three-quarters of American adults are overweight or obese and incur medical costs amounting to approximately USD 173 billion annually. Research has shown that GLP-1 RAs) substantially lower hemoglobin A1c levels, cardiovascular risk, and weight. However, to obtain sustained effects, they must be continued. Discontinuation could stem from efficacy, cost, tolerance, and access.

The effectiveness of GLP-1 RA is heterogeneous across patients. In many patients, weight loss plateaus, which could lead to discontinuation. Reinitiation and continuation could be driven by factors such as access to and affordability of GLP-1 RAs because obesity is more prevalent among individuals with low income. Supply-side constraints could also limit the continued use of GLP-1 RAs.

Previous research has largely ignored the magnitude of weight loss and the role played by GLP-1 RA discontinuation. Furthermore, the characterization of patterns of reinitiation after discontinuation is also poor.

About this study

The current study considers a sample of US adults who were overweight or obese and describes the rates of and factors driving the discontinuation of GLP-1 RAs. It also studies the dual gastric inhibitory polypeptide receptor–GLP-1 RAs labeled for both obesity and T2D (liraglutide, semaglutide, and tirzepatide). The heterogeneity among individuals with and without T2D was assessed. Finally, the study delves into factors and rates of reinitiation of these medications.

The data were derived from Truveta, which contains continuously updated and linked electronic health record (EHR) data from 30 US healthcare systems. Between January 1, 2018, and December 31, 2023, 125,474 adults were newly initiated treatment with a dual-labeled GLP-1 RA. The patients had a baseline body mass index (BMI) of 27 or more. They were followed up for up to 2 years to note discontinuation and for a further two additional years to note reinitiation.

At baseline, the patients were stratified by their T2D status. Kaplan-Meier models were used to estimate the proportions of discontinuation and reinitiation. Cox proportional hazards regression models were used to note the associations between proportions of discontinuation and reinitiation and sociodemographic characteristics.

Study findings

In the sample that met the inclusion criteria, 61% had T2D. Among them, 98.6% used anti-diabetes medications, and 1.4% were on antiobesity medications. Among the 39% without T2D, 61.8% used antidiabetes medications off-label, and 38.2% used antiobesity medications. The average age was about 54 years, and about 65% were female. Concerning race or ethnicities, 14.5% were Black or African American, 2.1% were Asian, 73.5% were White, 12.8% were Hispanic, and others formed the remaining sample.

It was noted that about 54% and 72% of patients discontinued their GLP-1 RA within 1 year and 2 years, respectively. For patients with T2D, the rates of discontinuation were significantly lower. In the sub-sample comprising patients followed up for the full 2 years, similar discontinuation rates were recorded. Concerning the factors significantly associated with higher discontinuation, age above 65 years and not having T2D were important.

Among those with T2D, higher-income individuals showed a lower rate of discontinuation. A significant association was also noted between lower discontinuation and greater on-treatment weight loss. Furthermore, patients with moderate or severe incident gastrointestinal adverse events were more likely to discontinue. Higher costs and adverse effects were the most frequent reasons for discontinuation, as per clinical notes.

A total of 41,792 patients were included in reinitiation analyses, with most being female, White, and not Hispanic or Latino. Post-primary discontinuation, the median follow-up time was 435 days. Within one year, 47.3% of patients with T2D and 36.3% of patients without T2D reinitiated a GLP-1 RA. The respective figures were 57.3% and 46.4% for reinitiation within 2 years of discontinuation.

Concerning factors associated with reinitiation, among those without T2D, the probability of reinitiation was significantly lower in individuals aged 65 years or older. There was a positive correlation between higher reinitiation and higher income, although this relationship was not always significant. Weight gain since discontinuation was also associated with a higher likelihood of reinitiation among patients with or without T2D. Finally, across both groups of patients, a lower rate of reinitiation was noted in the case of moderate or severe gastrointestinal adverse events during initial treatment.

Conclusions

In sum, the majority of overweight or obese patients discontinued GLP-1 RA therapy within one year. Higher discontinuation rates and lower reinitiation rates were recorded in those without T2D. Inequities in adherence and access to effective treatments could aggravate the disparities in obesity.