7918 Methadone Induced Hypoglycemia in a Patient with End-Stage Renal Disease

Disclosure: F. Anjum: None. S. Imtiaz: None. M.G. Jakoby: None. Introduction: Methadone is a synthetic opiate and mu-receptor agonist used for the treatment of opioid dependence. We report a case of methadone induced hypoglycemia in a patient with end-stage renal disease (ESRD) that resolved after reducing the dose of methadone. Case Presentation: A 49-year-old male with hemodialysis dependent ESRD presented to the emergency department with complaints of weakness and tremulousness and found to have a capillary blood glucose of 34 mg/dL. Medical history was notable for opioid dependence and two months of treatment with methadone 110 mg daily. The patient denied previous episodes of hypoglycemia, and no one in his household was prescribed insulin or insulin secretagogues. Since the patient had been treated with dextrose fluids before consultation, a diagnostic fast was performed. After 2 hours of fasting, the patient experienced neuroglycopenic symptoms, and plasma glucose fell to 55 mg/dL. Insulin level was 3 mIU/L (expected < 3), C-peptide 22.1 ng/mL (expected < 0.6), and proinsulin 7.4 pM (expected < 5). Beta-hydroxybutyrate level was 0.1 mM (expected > 2.7), and no drugs were detected on an insulin secretagogues panel. Methadone was reduced to 40 mg daily, and the patient had no additional hypoglycemic events on the lower methadone maintenance dose. Discussion: Methadone and tramadol are the two opiates reported to cause hypoglycemia in the FDA Adverse Events Reporting System. There is a clear relationship between methadone dose and hypoglycemia risk, with odds of hypoglycemia increased approximately three-fold at methadone doses of > 80 mg/d. Animal studies have linked the glucose lowering effects of methadone to mu-receptor activity, and the mu-receptor selective antagonist β-funaltrexamine blocks glucose lowering effects of the drug. It is not understood why other opioids (e.g. morphine) do not predispose to hypoglycemia. Mechanisms proposed for how methadone lowers blood glucose including increased insulin secretion, reduced gluconeogenesis, and suppression of counter-regulatory hormones. This patient was clearly hyperinsulinemic at time of hypoglycemia, and it unclear if impaired insulin clearance due to ESRD predisposed the patient to methadone induced hypoglycemia. Methadone is considered safe in ESRD due to limited accumulation as a result of fecal clearance of the drug. If hypoglycemia occurs during treatment with methadone, the dose should be reduced or methadone should be replaced with an alternative opioid. Presentation: 6/3/2024