medwireNews: A US study in JAMA Network Open reports high discontinuation rates of glucagon-like peptide (GLP)-1 receptor agonist therapy in adults with overweight or obesity, with rates lower in those with than without type 2 diabetes.
The researchers found that patients with overweight or obesity were significantly more likely to discontinue GLP-1 receptor agonists after a year of treatment if they did not have type 2 diabetes than if they did, at a rate of 64.8% versus 46.5%.
However, reinitiation of GLP-1 receptor agonists within the year was significantly more likely if people did have type 2 diabetes than if they did not, at respective rates of 47.3% and 36.3%.
Factors influencing discontinuation and reinitiation included weight gain or loss, gastrointestinal side effects, income, and age.
Ezekiel Emanuel, from the University of Pennsylvania in Philadelphia, USA, and colleagues examined discontinuation and reinitiation rates of GLP-1 receptor agonists, including liraglutide, semaglutide, and the dual GLP-1 receptor agonist/gastric inhibitory peptide tirzepatide, in 125,474 adults (mean age 54.4 years, 65.4% women) who were new users (within the preceding 2 months) of these medications between January 2018 and December 2023.
All the participants had a BMI of 27 kg/m2 or above (median 37.3 kg/m2), and 36.5% met criteria for class 3 obesity (BMI ≥40 kg/m2). In all, 61% of individuals had type 2 diabetes.
The researchers found that during up to 2 years of follow-up, 81,919 patients discontinued GLP-1 receptor agonist therapy, defined as a gap of 60 days. Just over half (53.6%) of the participants stopped within the first year and 72.2% by year 2. A significantly lower proportion of patients with type 2 diabetes than without had discontinued by 2 years, at 64.1% versus 84.4%.
The study showed that patients who lost more weight during therapy were less likely to discontinue treatment. For every 1% reduction in body weight, the likelihood of discontinuing GLP-1 receptor agonist therapy dropped by 3.1% in patients with type 2 diabetes and 3.3% in those without. This suggests that “weight management is an important factor regardless of type 2 diabetes status,” the investigators comment.
Other factors influencing adherence included moderate or severe gastrointestinal adverse events, which increased the likelihood of patients stopping GLP-1 receptor agonist therapy by 38% among individuals with type 2 diabetes and by 19% among those without. Being 65 years of age or older also significantly increased the likelihood of discontinuation, by 28% among those with diabetes and by 18% among those without.
Income had a “progressive effect,” the team notes, particularly for individuals with type 2 diabetes, with the lowest risk for discontinuation peaking among individuals earning more than US$ 80,000 (€ 77,493) per year, who were 28% less likely to discontinue therapy than individuals earning less than US$ 30,000 (€ 29,055) per annum.
Emanuel et al highlight that "greater efforts are needed to increase access and adherence” to GLP-1 receptor agonists among patients without type 2 diabetes and those with lower incomes.
Patients who discontinued treatment and had their weight measured within 60 days before stopping were tracked for another 2 years to evaluate reinitiation.
A total of 47.3% of those with type 2 diabetes and 36.3% of those without resumed therapy within 1 year. By year 2, reinitiation rates climbed to a corresponding 57.3% and 46.4%.
Weight regain after discontinuation strongly predicted reinitiation of GLP-1 receptor agonists. For every 1% increase in weight, the likelihood of resuming therapy rose by 2.3% in patients with type 2 diabetes and 2.8% in those without.
Older adults (≥65 years) were significantly less likely to restart therapy, with reinitiation rates 12% lower in those with type 2 diabetes, compared with their younger counterparts, and 27% lower in those without type 2 diabetes.
The authors conclude: “Our findings have important policy implications associated with equitable access and outcomes for patients with or without type 2 diabetes,” and add that “[i]nequities in access and adherence to effective treatments have the potential to exacerbate disparities in obesity.”
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