Evaluation of the counter-regulatory responses to hypoglycaemia in patients with type 1 diabetes during opiate receptor blockade with naltrexone

Sarita Naik, Renata Belfort-DeAguiar, Anne Sophie Sejling, Barbara Szepietowska, Robert S. Sherwin

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Aims: Hypoglycaemia is the major limiting factor in achieving optimal glycaemic control in people with type 1 diabetes (T1DM), especially intensively treated patients with impaired glucose counter-regulation during hypoglycaemia. Naloxone, an opiate receptor blocker, has been reported to enhance the acute counter-regulatory response to hypoglycaemia when administered intravenously in humans. The current study was undertaken to investigate the oral formulation of the long-acting opiate antagonist, naltrexone, and determine if it could have a similar effect, and thus might be useful therapeutically in treatment of T1DM patients with a high risk of hypoglycaemia. Materials and methods: We performed a randomized, placebo-controlled, double-blinded, cross-over study in which 9 intensively treated subjects with T1DM underwent a 2-step euglycaemic-hypoglycaemic-hyperinsulinaemic clamp on 2 separate occasions. At 12 hours and at 1 hour before the clamp study, participants received 100 mg of naltrexone or placebo orally. Counter-regulatory hormonal responses were assessed at baseline and during each step of the hyperinsulinaemic-clamp. Results: Glucose and insulin levels did not differ significantly between the naltrexone and placebo visits; nor did the glucose infusion rates required to keep glucose levels at target. During hypoglycaemia, naltrexone, in comparison with the placebo group, induced an increase in epinephrine levels (P =.05). However, no statistically significant differences in glucagon, cortisol and growth hormone responses were observed. Conclusion: In contrast to the intravenous opiate receptor blocker naloxone, overnight administration of the oral long-acting opiate receptor blocker, naltrexone, at a clinically used dose, had a limited effect on the counter-regulatory response to hypoglycaemia in intensively treated subjects with T1DM.

Original languageEnglish (US)
Pages (from-to)615-621
Number of pages7
JournalDiabetes, Obesity and Metabolism
Issue number5
StatePublished - May 2017
Externally publishedYes


  • counter-regulatory hormonal response
  • hypoglycaemia
  • naltrexone

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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