A comprehensive retrospective cohort study presented at the ENDO 2026 annual meeting has uncovered significant fluctuations in how patients utilize glucagon-like peptide-1 (GLP-1) receptor agonists. The research, which analyzed the treatment patterns of more than 60,000 Americans, suggests that the use of these blockbuster medications is far less linear than previously assumed by the medical community. While discontinuation rates for these drugs remain high, a substantial majority of patients eventually return to therapy, creating a "start-and-stop" cycle that carries profound implications for long-term chronic disease management.
Sainikhil Sontha, MS, a research associate at the Boston University School of Public Health and the study’s lead author, noted that while the popularity of GLP-1 medications has surged, the reality of patient adherence has remained a "black box" until now. The study sought to quantify two specific metrics: the rate at which patients with type 2 diabetes stop their GLP-1 regimens and the frequency with which they reinitiate them after a significant lapse in treatment.
Methodology and Study Parameters
To conduct the analysis, researchers utilized a massive dataset from Komodo Health, focusing on U.S. insurance claims recorded between January 2019 and June 2025. This timeframe is particularly significant as it encompasses the pre-pandemic era, the global COVID-19 health crisis, and the subsequent "boom" in GLP-1 popularity driven by both clinical success and social media visibility.
The study population consisted of adults aged 18 to 64 who met several specific criteria: a body mass index (BMI) of 25 kg/m² or higher, a diagnosis of type 2 diabetes, and a new prescription for one of three major GLP-1 medications—liraglutide, semaglutide, or tirzepatide. To ensure data integrity, participants were required to have been enrolled in their insurance plans for at least one year prior to starting the medication and to have at least six months of follow-up data available after the initial prescription.
For the purposes of the 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 following such a discontinuation. By using these parameters, the research team was able to track the longitudinal journey of patients over a multi-year period, providing a clearer picture of the real-world obstacles to consistent medication use.
The Discontinuation Crisis: Four in Ten Stop Within One Year
The data revealed a striking trend regarding treatment persistence. According to Sontha, approximately 40% of patients discontinued their GLP-1 medication within the first year of treatment. This figure grew as time progressed, with nearly 60% of patients stopping their therapy by the end of the second year.
The high rate of early discontinuation is a point of concern for endocrinologists and public health officials alike. GLP-1 medications, which mimic a hormone that targets areas of the brain that regulate appetite and food intake, require consistent blood-level maintenance to achieve their full metabolic benefits. When patients stop therapy prematurely, they risk the immediate return of glycemic instability and the cessation of weight loss progress.
Several factors were identified as primary drivers of this attrition. Using Cox proportional hazards models, the researchers adjusted for sociodemographic, clinical, and provider-level variables to determine which populations were most at risk. The findings highlighted significant disparities in healthcare delivery and patient experience.
Factors Driving Treatment Gaps: Side Effects and Socioeconomics
One of the most immediate barriers to adherence was found to be the medication’s side effect profile. Approximately 37% of patients who discontinued their medication within the first year cited nausea, vomiting, or other gastrointestinal issues. These "stomach-related" side effects are a well-documented characteristic of the GLP-1 class, often occurring during the titration phase as the body adjusts to the hormone-mimicking compounds.
Beyond clinical symptoms, socioeconomic factors played a decisive role in whether a patient stayed on their medication. The study found that patients insured through Medicaid or Medicare were significantly more likely to stop their GLP-1 therapy within the first 12 months compared to those with private insurance. This suggests that administrative hurdles, such as frequent prior authorization requirements, or fluctuations in coverage may be disrupting the continuity of care for lower-income populations.
Racial disparities also emerged as a critical factor. Black patients were found to be more likely to discontinue GLP-1 medications than their white counterparts. While the study did not explicitly detail the causes of this disparity, researchers pointed to a combination of systemic factors, including potential differences in pharmacy access, cost burdens, and variations in the patient-provider relationship.
The Reinitiation Trend: A "Start-and-Stop" Paradigm
Despite the high rates of discontinuation, the study offered a silver lining: many patients are not abandoning the drugs permanently. Instead, they appear to be caught in a cycle of intermittent use. The researchers found that 41.5% of those who stopped their medication restarted therapy within a year. By the two-year mark, nearly two-thirds (58%) of those who had discontinued had reinitiated treatment.
"This suggests that for many patients, these medications aren’t being abandoned permanently; use is more start-and-stop than most people assumed," Sontha explained during his presentation.
This reinitiation data suggests that while patients may find the medications difficult to maintain—whether due to cost, supply shortages, or side effects—they still recognize the clinical value of the treatment. The "revolving door" of GLP-1 use indicates a persistent demand for the health benefits these drugs provide, even if the logistics of daily or weekly administration prove challenging for the average patient.
The Influence of Medical Specialization and Drug Choice
The study also shed light on how the choice of medication and the type of prescribing physician influence long-term success. One of the most notable findings was the "endocrinologist effect." Patients whose first GLP-1 prescription was written by an endocrinologist were 10% less likely to stop their medication compared to those whose prescriptions came from general practitioners or other specialists.
This suggests that specialized care—which often includes more robust patient education on managing side effects and navigating insurance hurdles—plays a vital role in keeping patients on track. Endocrinologists may also be better equipped to manage the titration process, slowly increasing dosages to minimize the gastrointestinal distress that frequently leads to discontinuation.
Furthermore, the specific medication prescribed made a significant difference in adherence rates. Patients taking newer medications were far more likely to stay on therapy:
- Tirzepatide users were 41% less likely to discontinue their medication than those taking older drugs like liraglutide.
- Semaglutide users were 28% less likely to stop than those on older GLP-1 formulations.
The higher adherence rates for newer drugs like tirzepatide (marketed as Mounjaro for diabetes) and semaglutide (marketed as Ozempic for diabetes) may be attributed to their once-weekly injection schedules, which are less burdensome than the daily injections required for older drugs like liraglutide (Victoza). Additionally, the superior weight loss and A1c reduction associated with newer molecules may provide patients with more visible "positive reinforcement," encouraging them to persist despite side effects.
Clinical Implications and the Danger of Intermittent Use
The health implications of this "start-and-stop" pattern are profound. GLP-1 medications are not merely tools for weight management; they are powerful agents for preventing the long-term complications of type 2 diabetes.
"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."
Type 2 diabetes is a progressive disease, and the protective benefits of GLP-1s—including reduced cardiovascular inflammation and improved renal function—are cumulative. When a patient stops and starts therapy, they may experience "metabolic yo-yoing," where blood sugar levels and weight fluctuate, potentially negating some of the cardiovascular benefits gained during the periods of active treatment.
Analysis: A Call for Policy and Provider Support
The findings presented at ENDO 2026 serve as a call to action for the broader healthcare ecosystem. For insurers, the high rate of reinitiation suggests that restrictive "fail-first" policies or frequent re-authorizations may be counterproductive, leading to treatment gaps that eventually cost the system more in the form of acute diabetic complications.
For providers, the data underscores the necessity of the "endocrinology model" of care. Enhancing patient support systems—such as nurse-led follow-up calls during the first three months of therapy—could help mitigate the 37% of discontinuations caused by manageable side effects.
Finally, for policymakers, the study highlights a widening gap in health equity. If Black patients and those on Medicaid are disproportionately stopping these life-saving medications, then the current distribution and reimbursement models are failing to provide equitable access to the most effective treatments available.
As the medical community looks toward 2027 and beyond, the focus may shift from simply prescribing GLP-1s to ensuring that patients have the clinical, financial, and emotional support needed to stay on them. The "start-and-stop" era of GLP-1 use highlights a resilient patient desire for health improvement, but it also reveals a fragmented healthcare infrastructure that is not yet fully optimized for the longitudinal management of these transformative therapies.
