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Diabetes and Vascular Disease

SUN-579 - Methadone and Hypoglycemia in End-Stage Renal Disease: A Real-World Analysis

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT

    Late-Breaking Poster Presenter(s)

  • MA

    Meena Alzamani, MD

    University of Maryland Midtown Campus
    Baltimore, United States

    • Co-Author(s)

  • DC

    Damla N. Costa, MD

    University of Maryland Midtown Campus
    Halethorpe, United States

    • Senior Author/Primary Investigator(s)

  • KM

    Kashif M. Munir, MD

    University of Maryland School of Medicine
    Baltimore, United States



Introduction: Methadone carries a drug-specific risk of hypoglycemia, distinct from other opioids, mediated through gluconeogenesis impairment and insulin secretion. Patients with end-stage renal disease (ESRD) may be disproportionately vulnerable due to reduced renal gluconeogenesis and altered clearance, but no systematic data exist in this population.

Methods: Adult methadone-exposed patients with and without ESRD were identified from the TriNetX Global Collaborative Network (170 institutions), excluding hepatic failure, adrenal insufficiency, myxedema coma, and concurrent hypoglycemic agent use. Propensity score matching was performed on age, sex, BMI, malnutrition, chronic liver disease, and pre-existing hypoglycemia. The primary outcome was hypoglycemia (glucose ≤69 mg/dL or ICD-10 code E16.2) occurring after index methadone exposure. Kaplan-Meier, Cox regression, and number-of-instances analyses were conducted on unmatched and matched cohorts.

Results: A total of 2,259,762 methadone-exposed patients without ESRD and 21,081 with ESRD were identified. On multivariable Cox analysis adjusting for age, sex, BMI, pre-existing hypoglycemia, and liver disease, ESRD was an independent predictor of hypoglycemia (HR 2.31, 95% CI 2.23-2.40, p< 0.001), prompting propensity score matching on age, sex, BMI, malnutrition, liver disease, and pre-existing hypoglycemia (21,041 matched pairs). In the matched analysis, hypoglycemia occurred in 16% of ESRD patients versus 9.3% of controls (HR 1.99, 95% CI 1.88-2.10; p< 0.001). ESRD patients also experienced more recurrent hypoglycemic episodes (mean 2.73 vs. 2.11, p< 0.001).

Conclusions: ESRD substantially increases the risk of hypoglycemia among methadone-exposed patients, with more frequent recurrent episodes. These findings support targeted glucose monitoring and informed risk stratification in this high-risk population.

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