UMEM Educational Pearls

Category: Toxicology

Title: Methadone induced hypoglycemia Is there such a thing?

Keywords: methadone overdose, hypoglycemia (PubMed Search)

Posted: 1/26/2017 by Hong Kim, MD
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Methadone overdose produces classic signs and symptoms of opioid intoxication - CNS and respiratory depression with pinpoint pupils. However, methadone overdose has also been associated with hypoglycemia – a relatively uncommon adverse effect.

Bottom line:

  • Methadone-induced hypoglycemia can occur, although rare, in an acute overdose.


Several case reports have been published over the past years. Recently, a case of refractory hypoglycemia was reported in a woman, without a history of diabetes, after ingesting 250 mL of methadone (18.2 mg/kg).

She required, in additional to naloxone infusion for respiratory depression, dextrose infusion (initially D10 then D20) for 54 hours.

  • Plasma insulin levels were normal.
  • No oral hypoglycemic agents were detected in urine.
  • The exact mechanism of methadone-induced hypoglycemia is unknown.

Incidence of hypoglycemia has also been observed in patient with rapid methadone dose escalation as well as in cancer patient who were started on methadone for pain control with dose-depedent association. 

In a mice study, methadone induced a dose dependent hypoglycemia - 20 mg/kg methadone resulted in decrease in average glucose level of 172 +/- 7 mg/dL to 55 +/- 6 mg/dL. This effect was reversed by naloxone administration. morphine, fentanyl, oxycodone and levorphanol did not produce hypoglycemia.

However, in the case report published in Clinical Toxicology Nov 2016, naloxone infusion did not effect the hypoglycemia. 


  1. Li AT, Chu FK. A case of massive methadone overdose presented with refractory hypoglycemia. Clin Toxicol 2017 Jan 24:1-3. doi: 10.1080/15563650.2016.1277236. [Epub ahead of print]
  2. Moryl N et al. Hypoglycemia during rapid methadone dose escalation. J Opioid Manag. 2013;9:29-34.
  3. Flory JH et al. Methadone use and the risk of hypoglycemia for inpatients with cancer pain. J Pain Symptoms Manage 2016;51:79-87.
  4. Faskowtiz AJ et al. Methadone-induced hypoglycemia. Cell Mol Neurobiol 2013;33:537-42.