Just over half of patients with overweight or obesity discontinued their GLP-1 receptor agonist within 1 year, with rates even higher among the subset without type 2 diabetes, according to a retrospective cohort study.
Among over 125,000 patients, 53.6% discontinued their GLP-1 receptor agonist by 1 year, and these rates were significantly higher for patients without versus with type 2 diabetes (64.8% vs 46.5%), reported Ezekiel J. Emanuel, MD, PhD, of the University of Pennsylvania in Philadelphia, and colleagues.
Regardless of diabetes status, every 1% of body weight loss was tied to a 3% lower risk of discontinuation, they wrote in JAMA Network Open.
Of the 41,792 patients who stopped treatment and had a weight measurement at discontinuation available, 47.3% and 36.3% of those with and without type 2 diabetes, respectively, restarted their GLP-1 agent at 1 year, and 57.3% and 46.4% restarted within 2 years. For every 1% of body weight regained after discontinuing treatment, there was a 2% to 3% increased hazard of restarting treatment.
The high discontinuation rate did not come as much of a surprise, as prior studies have reported GLP-1 receptor agonist discontinuation rates of up to 81%, Emanuel's group wrote. They added that the links between weight loss and discontinuation and between weight regain and reinitiation "suggest that weight management is an important factor regardless of type 2 diabetes status."
In a statement, co-author Ty Gluckman, MD, MHA, of Providence Heart Institute in Portland, Oregon, said that "improved understanding of the factors related to discontinuation and reinitiation of GLP-1 receptor agonists is essential for personalizing treatment to each patient's unique health needs and circumstances. These insights allow us to identify barriers and align treatment plans with patients' goals and lifestyles."
"Equally important is fostering a strong partnership between patients and their clinical teams, ensuring open communication and shared decision making," he added. "This collaborative approach empowers patients to achieve the best possible outcomes and receive the care they truly deserve."
Because poor adherence to GLP-1 receptor agonists may limit the long-term health benefits like cardiovascular risk reduction, the researchers called for increased access for lower-income patients.
"Given the huge obesity and diabetes epidemics in the U.S., access to GLP-1 medications is a public health priority," Emanuel said in a statement. "Their potential is only realized if patients can afford and access them."
For this study, the researchers included 125,474 new users of liraglutide (Victoza, Saxenda), semaglutide (Ozempic, Wegovy), or tirzepatide (Mounjaro, Zepbound) -- all of which hold indications for type 2 diabetes and chronic weight management -- between January 2018 and December 2023. Median duration of primary treatment was 176 days, and the most commonly used agent was semaglutide (72.1%), followed by liraglutide (14.3%), and tirzepatide (13.6%).
All patients had to have newly initiated a GLP-1 agent, a baseline body mass index (BMI) of at least 27, and regular interactions with healthcare in the prior year. Mean age was 54.4, 65.4% were women, 73.5% were white, and median baseline BMI was 37.3.
Of the included patients, 61% had type 2 diabetes; 98.6% of these patients were using anti-diabetes medications and 1.4% were using anti-obesity medications.
Two other factors were significantly associated with a greater likelihood of discontinuing treatment for those with and without type 2 diabetes:
- Age 65 and older: HR 1.28 (95% CI 1.24-1.32) and HR 1.18 (95% CI 1.13-1.22)
- Moderate or severe incident gastrointestinal adverse events: HR 1.38 (95% CI 1.31-1.45) and HR 1.19 (95% CI 1.12-1.27)
On the other hand, a higher income was progressively associated with a lower rate of discontinuation among those with type 2 diabetes, and there was a similar trend in those without diabetes. Of note, patients without type 2 diabetes had higher baseline incomes.
"Adverse effects and cost were the most frequent specific reasons for discontinuation documented in clinical notes," the researchers pointed out.
Not surprisingly, a higher income was also associated with a higher likelihood of treatment reinitiation, while gastrointestinal events were tied to a lower likelihood of reinitiation.
"This study sheds light on the challenges for real-world patients of staying on these medications and highlights the need to tackle barriers such as cost, insurance coverage, and equitable policies to ensure availability," Emanuel said. "Without these measures, we risk widening health disparities and denying countless individuals the chance to improve their health and quality of life."
One limitation to the study was the researchers' inability to adjust for GLP-1 receptor agonist shortages, which persisted for years and are only recently starting to resolve. In addition, medication rationing was not considered in the analysis.
Disclosures
Emanuel reported relationships with the University of California San Francisco, Advocate Aurora Health, Cain Brothers, Bowdoin College, the Suntory Foundation, Ontario Hospital Association, University of Oklahoma, Sanford Health, Health Plan Alliance, Emory Health Care, Employer Direct Health Care, Galien Foundation, HLTH Inc, National University of Singapore, Hawaii Medical Services Association, Tel Aviv University, the Quadrangle, Lazard, University of Bergen, University of Virginia, New York Historical Society, Amangiri, Forerunner Conference, BCEPS International Symposium, Future of Science, Cell and Gene Therapy, Arendalsuka Meeting, Cellares Corp, Clarify Health Solutions, Notable Health, JSL Health, Peterson Center of Healthcare, the World Health Organization (WHO), the Expert Advisory Group WHO COVID-19 committee, HIEx Health Innovation Exchange Partnership sponsored by the United Nations, the WHO Expert Group on Ethics & Governance of Outbreaks/Emergencies, the WHO Guideline Development Group on the Use and Indications of GLP-1s for Adults Living With Obesity, the Internal Advisory Board of the Penn Parity Center, Link Health Technologies, Nuna Health, Alto Pharmacy, Korro/Coach AI, Aberdeen Inc, FeelBetter Inc, Biden's Transition COVID-19 Committee, and member of the JAMA Editorial Board.
No other disclosures were reported.
Primary Source
JAMA Network Open
Source Reference: Rodriguez PJ, et al "Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists among US adults with overweight or obesity" JAMA Netw Open 2025; DOI: 10.1001/jamanetworkopen.2024.57349.
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