A comprehensive retrospective cohort study presented at the ENDO 2026 annual meeting has unveiled significant fluctuations in how patients utilize glucagon-like peptide-1 (GLP-1) receptor agonists, suggesting that the clinical reality of these "blockbuster" drugs is far more intermittent than previously characterized. The research, which analyzed insurance claims from more than 60,000 Americans, indicates that while a majority of patients eventually pause their treatment, a substantial percentage return to the therapy within two years, creating a "start-and-stop" cycle that presents new challenges for long-term chronic disease management.
The study, led by Sainikhil Sontha, MS, a research associate at the Boston University School of Public Health, addressed two critical but previously under-researched questions: the definitive rate of discontinuation among type 2 diabetes patients and the frequency with which these patients reinitiate therapy. By tracking a massive dataset of patients using liraglutide, semaglutide, and tirzepatide, the research team provided a high-resolution look at the longitudinal behavior of patients navigating the complexities of modern metabolic medicine.
The Dynamics of Adherence: A Multi-Year Analysis
The findings presented at ENDO 2026 challenge the traditional pharmaceutical model of "linear adherence," where a patient is expected to remain on a chronic medication indefinitely. According to Sontha’s data, approximately 40% of patients prescribed a GLP-1 medication for type 2 diabetes stopped their treatment within the first 12 months. This number climbed to nearly 60% by the end of the second year.
However, the study also uncovered a resilient trend in reinitiation. Among those who discontinued their medication—defined as having a gap in fills exceeding 60 days—41.5% restarted the therapy within one year. By the second year, nearly two-thirds (58%) of those who had stopped were back on a GLP-1 regimen.
"This suggests that for many patients, these medications aren’t being abandoned permanently," Sontha noted during the presentation. "Use is more start-and-stop than most people assumed." This cyclical pattern suggests that patients may be viewing these medications as tools to be used intermittently, or perhaps more likely, that external factors such as cost, supply, and side effects are forcing temporary pauses rather than permanent cessation.
Methodology and Study Chronology
The researchers utilized an expansive dataset from Komodo Health, covering U.S. insurance claims from January 2019 through June 2025. This six-year window allowed the team to capture the period of greatest growth for the GLP-1 class, including the rise of semaglutide (Ozempic/Wegovy) and the introduction of tirzepatide (Mounjaro/Zepbound).
The study cohort was strictly defined to ensure clinical relevance. Participants were adults aged 18 to 64 with a body mass index (BMI) of at least 25 kg/m² and a documented diagnosis of type 2 diabetes. All participants had at least six months of follow-up data and had been enrolled in their insurance plans for at least one year prior to starting the medication. This rigor allowed the researchers to account for prior health history and ensure that the "discontinuation" was not merely a result of a patient switching insurance providers or losing coverage.
By employing Cox proportional hazards models, the team was able to adjust for a variety of variables, including sociodemographic factors, clinical history, and the specific type of healthcare provider who issued the initial prescription.
Predictors of Discontinuation: Socioeconomic and Clinical Barriers
One of the most significant aspects of the study was its identification of the predictors that lead to treatment gaps. The data revealed a stark divide along socioeconomic and racial lines. Patients enrolled in Medicaid or Medicare were significantly more likely to discontinue their GLP-1 medications within the first year compared to those with private commercial insurance.
Racial disparities also emerged as a primary factor. Black patients were found to have higher rates of discontinuation, a finding that researchers suggest may be linked to broader systemic issues including pharmacy deserts, higher out-of-pocket costs, and historical inequities in healthcare access.
Clinical side effects remained a major hurdle. Approximately 37% of patients who stopped their medication cited nausea or other gastrointestinal issues as the primary reason. This aligns with long-standing clinical observations regarding the GLP-1 class, which is known for causing "gastric slowing" that can lead to discomfort, particularly during the dose-escalation phase.
The Impact of Specialist Care and Medication Type
While socioeconomic factors often hindered adherence, the study identified two major "protective" factors that helped patients stay on their prescriptions.
First, the type of prescribing physician played a measurable role. Patients whose first GLP-1 prescription was written by an endocrinologist were 10% less likely to stop the medication compared to those whose prescriptions came from general practitioners or other specialists. This suggests that the specialized counseling, titration management, and expectation-setting provided by endocrinologists may be vital in helping patients navigate the initial side-effect profile of the drugs.
Second, the specific generation of the medication influenced longevity. Patients on newer, more potent medications showed much higher persistence rates:
- Tirzepatide: Users were 41% less likely to discontinue than those on older drugs like liraglutide.
- Semaglutide: Users were 28% less likely to discontinue than those on older formulations.
The researchers hypothesize that the increased efficacy of newer agents—which offer superior blood glucose control and more significant weight loss—may provide more "positive reinforcement" for the patient, making them more willing to tolerate side effects or navigate insurance hurdles.
Background Context: The GLP-1 Revolution (2019–2026)
To understand the significance of this study, one must look at the timeline of the GLP-1 market. Between 2019 and 2025, the pharmaceutical landscape for type 2 diabetes and obesity underwent a radical transformation. In 2019, liraglutide (Victoza) was the established standard, but it required daily injections. The shift toward weekly semaglutide injections revolutionized the market, followed by the 2022 approval of tirzepatide, a dual agonist that targets both GLP-1 and GIP receptors.
During the study’s timeframe, global supply chain shortages also plagued the industry. From 2022 through 2024, many patients were forced to stop their medication not because of choice or side effects, but because pharmacies simply could not stock the drugs. This external "forced discontinuation" likely contributes to the high "restart" rates found in the study, as patients returned to the medication as soon as supply stabilized.
Implications for Public Health and Policy
The "start-and-stop" nature of GLP-1 use has profound implications for long-term health outcomes. "Consistent use of these medications is what produces their protective effects," Sontha emphasized. "Stopping early may mean missed opportunities to prevent heart attacks, kidney disease progression, and other complications."
Type 2 diabetes is a progressive disease. GLP-1s have been shown in landmark trials, such as the SOUL and FLOW trials, to significantly reduce the risk of major adverse cardiovascular events (MACE) and chronic kidney disease (CKD). However, these benefits are cumulative and contingent on metabolic stability. A "yo-yo" pattern of medication use could potentially lead to "metabolic rebound," where blood sugar levels and weight spike during off-periods, potentially straining the cardiovascular system.
For insurers and policymakers, the study provides a roadmap for where intervention is most needed. The high discontinuation rate among Medicaid and Medicare recipients suggests that current coverage models may be too restrictive or that the "prior authorization" process creates barriers that lead to treatment gaps. Furthermore, the 10% improvement in adherence seen with endocrinologists suggests that increasing access to specialists—or providing better GLP-1 training for primary care physicians—could improve national health outcomes.
Expert Reactions and Future Outlook
While the study focused on type 2 diabetes, the implications extend to the broader "anti-obesity medication" (AOM) market. Industry analysts suggest that if similar start-and-stop patterns exist among those taking these drugs solely for weight loss, the long-term "return on investment" for insurers could be called into question.
Medical experts attending ENDO 2026 noted that the study highlights a need for better "persistence programs." These might include digital health tools to help patients manage nausea, or more flexible dosing schedules that allow patients to remain on a lower, more tolerable dose rather than discontinuing entirely when side effects become unmanageable.
As the medical community moves toward 2027 and beyond, the focus is expected to shift from "who should get these drugs" to "how do we keep them on these drugs." The Boston University study serves as a critical baseline, proving that while the demand for GLP-1 medications is unprecedented, the path to consistent, long-term therapy remains fraught with clinical, financial, and systemic obstacles.
The researchers hope that by identifying the specific populations at risk of stopping—namely Black patients and those on public insurance—healthcare systems can develop targeted support structures to ensure that the "miracle drugs" of the 2020s deliver on their promise of lifelong health improvement.
