A signal of increased risk of hypoglycaemia with angiotensin receptor blockers caused by confounding

Br J Clin Pharmacol. 2008 Jul;66(1):142-5. doi: 10.1111/j.1365-2125.2008.03176.x. Epub 2008 May 27.

Abstract

Aims: To study reporting of hypoglycaemia in angiotensin receptor blocker (ARB) users, and to investigate the possibility of confounding.

Methods: The French pharmacovigilance database was examined for an association between hypoglycaemia and ARBs or other drugs using reports notified between 1996 and 2005. This association was also tested in patients taking or not taking antidiabetic agents (ADAs) using reporting odds ratios (ROR).

Results: Hypoglycaemia was mentioned in 807 of the 174 595 reports entered during the study period. Overall hypoglycaemia was associated with the use of ARBs [ROR 2, 95% confidence interval (CI) 1, 3] and with the use of ADAs (ROR 32, 95% CI 27, 37). Moreover, the use of ARBs was associated with the use of ADAs (OR 7, 95% CI 6, 8). Considering separately reports with and without ADA, the association of ARB use with a higher risk of hypoglycaemia disappeared (OR 0.4, 95% CI 0.2, 0.8 and OR 2, 95% CI 1, 3, respectively).

Conclusion: A signal indicating an association between ARB use and hypoglycaemia was found in the French pharmacovigilance database. This signal disappeared after stratification on ADA use, thus suggesting confounding by indication. Moreover, the association between ARB use and hypoglycaemia was negative in ADA users.

MeSH terms

  • Adverse Drug Reaction Reporting Systems
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Databases, Factual
  • France
  • Humans
  • Hypoglycemia / chemically induced*
  • Hypoglycemia / epidemiology
  • Hypoglycemic Agents / therapeutic use*
  • Odds Ratio
  • Risk Factors

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Hypoglycemic Agents