A majority of people with overweight or obesity prescribed glucagon-like peptide 1 receptor agonists (GLP-1 RAs) discontinue them within 1 year, with higher quit rates among those without type 2 diabetes (T2D), new research suggested.
The data, from electronic health records of more than 125,000 adults who initiated GLP-1 RA treatment in the United States, showed that just over half stopped using GLP-1 RAs at 1 year. More than two thirds of those without T2D did so compared with just under half of those with T2D.
In addition, people without T2D were also less likely to reinitiate GLP-1 RAs within a year after stopping them. Weight loss, income, and adverse events were significantly associated with discontinuation, while weight regains predicted GLP-1 RA reinitiation.
Previous studies have examined rates of GLP-1 RA discontinuation, but this is believed to be the first to look at reinitiation, as well as to explore the possible reasons that patients stop and restart the drugs, first author Patricia J. Rodriguez, PhD, told Medscape Medical News.
“GLP-1 medications have changed the way doctors treat type 2 diabetes and obesity…This research, with real-world data, aimed to improve our understanding of how these medications are being used in everyday practice and the barriers patients may face to sustained use,” said Rodriguez, principal applied research scientist at Truveta, Inc., Bellevue, Washington, a collective of US health systems from which the data were obtained.
“I think these findings really highlight the need for clinical teams and patients to work together to assess the patient's needs and to tailor a treatment plan to address some of the barriers that might exist to continued medication-taking behavior and that could involve side effects, affordability, or weight loss,” Rodriguez said.
In a statement provided to Medscape Medical News, the study’s senior author, Ezekiel Emanuel, MD, PhD, co-director of the Healthcare Transformation Institute, University of Pennsylvania, Philadelphia, said, “These insights emphasize the need for policy changes to improve insurance coverage for individuals without T2D, as well as strategies to manage side effects and enhance patient adherence. Personalized treatment plans that incorporate patient-specific weight loss goals and financial assistance programs may help improve long-term adherence.”
Asked to comment, Hamlet Gasoyan, PhD, an investigator at the Center for Value-Based Care Research, Cleveland Clinic, Cleveland, who has also published on GLP-1 RA discontinuation, told Medscape Medical News that the new data align with his prior findings of high overall discontinuation rates and the greater likelihood of discontinuation among those without T2D.
“Their results are consistent with our finding that patients experiencing greater medium-term weight loss have a higher likelihood of persisting with obesity pharmacotherapy,” Gasoyan added.
He called the high discontinuation rate among patients without T2D “striking,” as well as “reinforcing concerns that insurance barriers limit sustained use for those seeking GLP-1 RAs for weight management. Additionally, the study found that weight gain after stopping was strongly associated with reinitiation, suggesting that many patients may need long-term therapy to maintain weight loss.”
And, Gasoyan pointed out, “While insurance status was not available to the study authors, they used age 65 years or older as a proxy for Medicare eligibility, which was again associated with the likelihood of GLP-1 RA discontinuation. The stark differences in discontinuation and reinitiation rates between those with and without type 2 diabetes are likely due to the differences in insurance coverage for these medications based on treatment indication.”
Quitting and Restarting Patterns
The findings came from Truveta Data, which compiles and continuously updates electronic health record data from 30 US healthcare systems, including drug prescribing and dispensing, clinical and demographic data, and clinical notes, as well as linkages to other data including social determinants of health.
The study population included 125,474 adults with overweight or obesity who initiated a GLP-1 RA (liraglutide, semaglutide, or tirzepatide) between January 1, 2018, and December 31, 2023. Of those, 61% (76,524) had T2D, while 39% (48,950) did not. Overall, 112,634 were followed up for at least 1 year and 48,099 for at least 2 years.
A total of 53.6% discontinued GLP-1 RAs by 1 year and 72.2% by 2 years. “There's so much interest in these medications, so finding that the majority of patients stopped them within a year was surprising to us,” Rodriguez commented.
However, 1-year discontinuation rates were significantly lower among those with T2D, just 46.5% compared with 64.8% for those without T2D. At 2 years, those rates were 64.1% vs 84.4%, respectively.
Factors significantly associated with discontinuation included age 65 years or older, with hazard ratios of 1.28 among those with T2D and 1.18 among those without. Higher income was progressively associated with a lower likelihood of discontinuation among those with T2D, with a hazard ratio of 0.72 for those with incomes greater than $80,000 vs under $30,000.
Greater weight loss while on GLP-1 RA treatment also predicted a lower likelihood of quitting the drugs, with a 1% weight reduction associated with a 3.1% lower likelihood of discontinuation among those with T2D and a 3.3% lower rate among those without T2D.
Moderate or severe gastrointestinal (GI) events also predicted discontinuation, both for those with T2D (hazard ratio, 1.38) and those without (hazard ratio, 1.19). According to the clinical notes, side effects were the most common reason for discontinuation among those with T2D, whereas “too expensive” was more common among those without T2D.
Of the total 81,919 patients who had discontinued taking GLP-1 RAs, 51.0% (41,792) were included in a reinitiation analysis. The rates of reinitiation within 1 year of discontinuation were 47.3% of those with T2D vs 36.3% of those without.
Factors significantly associated with reinitiation were a lower likelihood among those aged 65 years or older (hazard ratio, 0.88) and a 1% weight gain since discontinuation, which was associated with a 2.3% increased likelihood of reinitiation among those with T2D and a 2.8% increased likelihood among those without T2D.
Moderate or severe GI adverse events during initial treatment predicted a lower likelihood of reinitiation among those with and without T2D (hazard ratios, 0.86 and 0.82, respectively).
Gasoyan commented, “As more data become available on the reasons for treatment discontinuation with novel GLP-1 RA medications and how early or late discontinuation with these medications impacts clinical outcomes in real-world settings, clinicians will be better equipped to discuss these aspects with their patients and help to choose the best treatment option for them.”
The findings were published online on January 31, 2025, in JAMA Network Open.
Rodriguez is an employee of Truveta, Inc. Gasoyan received grant support from the National Cancer Institute. Emanuel reported receiving personal fees from 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 Healthcare, and Employer Direct Healthcare; nonfinancial support from Galien Foundation, HLTH, Inc., National University of Singapore, Hawaii Medical Service 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, and Arendalsuka Meeting during the conduct of the study; and serving as a member of the Board of Advisors for Cellares Corp, advisor for Clarify Health Solutions, advisor for Notable Health, member of the Advisory Board for JSL Health, member of the Advisory Board for Peterson Center on Healthcare, special advisor to the Director General of the World Health Organization (WHO), member of the Expert Advisory Group WHO COVID-19 Committee, member of the Advisory Board of the HIEx Health Innovation Exchange Partnership sponsored by the United Nations, member of the WHO Expert Group on Ethics and Governance of Outbreaks/Emergencies, member of the WHO Guideline Development Group on the Use and Indications of GLP-1s for Adults Living With Obesity, member of the Internal Advisory Board of The Penn Parity Center, advisor for Link Health Technologies, advisor for Nuna Health, member of the Board of Advisors of Alto Pharmacy, consultant for Korro/Coach AI, consultant for Aberdeen, Inc., member of the Advisory Board of FeelBetter, Inc., member of the Advisory Board of Biden’s Transition COVID-19 Committee, and member of the JAMA Editorial Board.
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