Comparative study of hypoglycaemia induced by opioids. Is it a class effect?

ABSTRACT

Objective: Drug-induced hypoglycaemia has been described with the use of tramadol and methadone. The authors aimed to determine if drug-induced hypoglycaemia could be a class effect for opioids.

Methods: The authors performed a disproportionality analysis in VigiBase®, the WHO global individual case safety report database with nine opioids (codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, tramadol, buprenorphine and nalbuphine) using the broad Standardised MedDRA Query for hypoglycaemia. The authors also carried out a descriptive study of opioid-induced hypoglycaemia in the French PharmacoVigilance DataBase (FPVDB) using the MedDRA Preferred Term ‘hypoglycaemia’.

Results: The global adjusted Reporting Odds Ratio (aROR) value for the 9 opioids was 1.53 (95% CI 1.52–1.54). The aROR ranged from 1.09 to 1.97 depending on the opioid, but all were statistically significant. A sex ratio of 0.74 was found for the reports of opioid-induced hypoglycaemia in Vigibase®. The authors also found 133 reports of hypoglycaemia in the FPVDB related to opioids. Among the reports, 55 were glycaemic imbalances in diabetics occurring shortly after the start of opioid treatment.

Conclusion: This work highlighted a significant association between all opioids and hypoglycaemia, thereby indicating that opioid-induced hypoglycaemia is probably a class effect. Women and/or diabetics seem to be more at risk for developing opioid-induced hypoglycaemia.

KEYWORDS:

• Opioids
• hypoglycaemia
• adverse effects
• safety
• database
• disproportionality analysis

Acknowledgments

The information presented in this study does not represent the opinion of WHO. The authors thank the custom searches team at the Uppsala Monitoring Centre (Uppsala, Sweden) research section, without whom this study would not have been possible.

Authors’ contributions

Conception and design: B Chrétien and X Humbert. Data analysis: B Chrétien and C Dolladille. Data interpretation and drafting of the paper: B Chrétien, X Humbert, C Dolladille and J Alexandre. Critical revision: all. Final approval: all. All authors agree to be accountable for all aspects of the work.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.