The clinical landscape for managing type 2 diabetes and obesity has been fundamentally altered by the advent of glucagon-like peptide-1 (GLP-1) receptor agonists, yet new data suggests that patient adherence to these regimens is far more volatile than previously understood. Research presented at the ENDO 2026 annual meeting indicates that while GLP-1 medications are highly effective, a significant portion of the patient population experiences a "start-and-stop" relationship with the therapy. The study, which utilized a massive longitudinal dataset of insurance claims, reveals that while discontinuation rates are high within the first two years of treatment, a substantial number of patients eventually return to the medication, suggesting that treatment journeys are rarely linear.
Sainikhil Sontha, MS, a research associate at the Boston University School of Public Health, led the investigation into these patterns of use. The research sought to address two critical gaps in medical literature: the precise rate at which patients with type 2 diabetes stop using GLP-1 medications and the frequency with which they reinitiate therapy after a lapse. According to Sontha, the findings challenge the assumption that stopping a GLP-1 medication represents a permanent abandonment of the treatment. Instead, the data points toward a cyclical usage pattern influenced by side effects, drug availability, and the specific type of medication prescribed.
Methodology and Study Framework
The researchers conducted a comprehensive retrospective cohort study leveraging data from Komodo Health, a major U.S. healthcare technology company that tracks insurance claims. The study period spanned from January 2019 to June 2025, providing a robust six-year window that captured the surge in GLP-1 popularity and the introduction of newer-generation dual-agonist therapies.
The study population was restricted to adults aged 18 to 64 years with a Body Mass Index (BMI) of 25 kg/m² or higher and a confirmed diagnosis of type 2 diabetes. To ensure data integrity, the participants were required to have been enrolled in their insurance plans for at least one year prior to starting treatment and to have at least six months of follow-up data available. The medications analyzed included liraglutide (an older, daily injectable), semaglutide (a weekly injectable or daily pill), and tirzepatide (a newer dual GLP-1 and GIP receptor agonist).
For the purposes of this study, "discontinuation" was strictly defined as a gap of more than 60 days in filling a GLP-1 prescription. Conversely, "reinitiation" was defined as the act of obtaining a new fill after such a gap had occurred. By using these parameters, the researchers were able to quantify the ebb and flow of patient adherence with a high degree of precision.
The Reality of Discontinuation: A Two-Year Perspective
The findings presented at ENDO 2026 underscore a significant challenge in long-term chronic disease management. Using insurance records from more than 60,000 Americans, the research team found that approximately 40% of patients discontinued their GLP-1 medication within the first 12 months of therapy. The attrition continued into the second year, with nearly 60% of patients having stopped their medication by the 24-month mark.
These figures are particularly striking given the clinical benefits associated with these drugs, which include not only glycemic control and weight loss but also significant reductions in cardiovascular and renal risks. The high rate of early discontinuation suggests that barriers to long-term use—whether physiological, financial, or logistical—remain formidable for a large segment of the population.
However, the study also uncovered a "revolving door" phenomenon. Of the patients who discontinued their medication, 41.5% restarted therapy within a year. By the end of two years, 58% of those who had previously stopped had reinitiated their treatment. Sontha noted that this suggests a level of patient persistence that is often overlooked. For many, the decision to stop is not a rejection of the drug’s efficacy, but rather a temporary pause, potentially necessitated by external factors such as insurance coverage changes or supply chain shortages.
Predictors of Adherence: Medication Type and Provider Influence
The study utilized Cox proportional hazards models to identify which factors most strongly predicted whether a patient would stay on their medication or stop. One of the most significant findings was the disparity between older and newer classes of GLP-1 drugs.
Patients prescribed tirzepatide, a newer medication that targets both GLP-1 and GIP receptors, were 41% less likely to discontinue treatment compared to those taking liraglutide. Similarly, semaglutide users were 28% less likely to stop their medication than those on the older liraglutide. This suggests that the improved efficacy and potentially more manageable side-effect profiles of newer medications are contributing to better patient retention.
The role of the prescribing physician also emerged as a critical factor in patient success. The data revealed that patients were 10% less likely to stop their medication if their initial prescription came from an endocrinologist rather than a general practitioner or other specialist. This finding highlights the importance of specialized care in managing the nuances of GLP-1 therapy, including the management of side effects and the titration of dosages.
Socioeconomic Disparities and Clinical Barriers
The research highlighted a troubling trend regarding health equity. Patients enrolled in Medicaid or Medicare, as well as Black patients, were found to be significantly more likely to discontinue GLP-1 medications within the first year. These findings point toward systemic barriers, including potential issues with consistent access to pharmacies, the high cost of co-pays for those on public insurance, and broader socioeconomic stressors that can interfere with chronic disease management.
Clinical side effects also played a major role in the "start-and-stop" cycle. Approximately 37% of patients who discontinued their medication reported experiencing nausea or other gastrointestinal issues. While these side effects are well-documented characteristics of the GLP-1 class, the study confirms that they remain a primary driver of treatment interruption.
Chronology of the GLP-1 Evolution (2019–2025)
To understand the context of the study, it is necessary to look at the timeline of GLP-1 development and market penetration during the study period:
- 2019–2020: The market was dominated by liraglutide and early versions of semaglutide. Usage was primarily focused on type 2 diabetes management with secondary interest in weight loss.
- 2021: The FDA approval of higher-dose semaglutide for chronic weight management sparked a global surge in interest, leading to the first major waves of supply shortages.
- 2022–2023: Tirzepatide entered the market, showing superior weight loss results in clinical trials. During this period, "off-label" use became a mainstream phenomenon, complicating insurance coverage and supply for patients with type 2 diabetes.
- 2024–2025: The period covered by the end of the study’s data saw increased competition, the introduction of oral versions of these drugs, and more aggressive utilization management by insurers, which likely contributed to the 60-day fill gaps observed in the data.
Expert Analysis and Industry Implications
The implications of this research are far-reaching for healthcare providers, insurers, and the pharmaceutical industry. The "start-and-stop" nature of GLP-1 use suggests that the current model of prescribing—which often assumes a continuous, lifelong commitment—may not align with the reality of patient experiences.
From a clinical perspective, inconsistent use is a major concern. "This research matters because 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." When a patient stops and restarts, they may also have to undergo the dose-titration process again to minimize side effects, which can delay the achievement of therapeutic goals.
For insurers and policymakers, the high rate of reinitiation suggests that restrictive "fail-first" policies or frequent re-authorization requirements may be counterproductive. If more than half of patients who stop eventually return to the drug, the administrative hurdles intended to control costs may instead be creating the very gaps in care that lead to expensive complications like hospitalizations for diabetic ketoacidosis or cardiovascular events.
Looking Ahead: Enhancing Patient Support
The researchers hope that these findings will serve as a call to action for the medical community to provide more robust support for patients starting GLP-1 therapies. Because the first year is the most volatile period for adherence, targeted interventions during this window—such as more frequent check-ins with endocrinologists or specialized pharmacists—could help patients manage side effects and navigate insurance hurdles.
Furthermore, the data suggests a need for more stable supply chains. While the study did not explicitly track drug shortages, the 2022-2025 period was marked by significant "Ozempic" and "Mounjaro" scarcities. It is highly probable that a portion of the "discontinuations" observed in the insurance data were involuntary, caused by patients being unable to find their medication in stock.
As the medical community moves toward 2027 and beyond, the focus will likely shift from simply prescribing these "blockbuster" drugs to ensuring that patients can stay on them. The ENDO 2026 presentation makes it clear that while GLP-1 medications are a powerful tool in the fight against diabetes and obesity, their success depends on a healthcare system that can support patients through the complexities of long-term adherence. Reducing the "start-and-stop" cycle will be essential to realizing the full public health potential of these therapies.
