Ibuprofen and risk of hypoglycemia in diabetic and non-diabetic consumers: analysis of international pharmacovigilance data

Introduction: Ibuprofen was associated with hypoglycemia in a single published case report in a diabetic patient. Ibuprofen, however, has never been associated so far with hypoglycemia in previously healthy non-diabetic individuals and thus, it is not listed as adverse effect in its summary of product characteristics approved by major regulatory authorities. Objective: This study was conducted to assess the causal relationship between ibuprofen and hypoglycemia in diabetic and non-diabetic individuals. Materials and Methods: Analysis of the literature and the WHO global database of individual case safety reports, VigiBase, was made to explore evidence on the association of ibuprofen and hypoglycemia. The unpublished data and the currently availablepublished toxicological, biological, clinical and epidemiological evidence, if any, was systematically organized using Austin Bradford Hill criteria, causality assessment framework, to assess the causal link between ibuprofen and hypoglycemia. Results: In VigiBase, there were 125 cases of hypoglycemia associated with ibuprofen, reported from 19 countries. About 50% had history of diabetes. Ibuprofen was reported as sole suspect in 36.8% of the cases and the only drug administered in18.4%. Hypoglycemia resolved following discontinuation of ibuprofen in 21.6% and recurred in three patients with rechallenge. Outcome was fatal in 10.5%. Where ibuprofen was solely administered, median time-to-onset of hypoglycemia was one-day following administration of the drug. In an experimental study, a significant decrease in blood glucose level was observed at a higher dose of ibuprofen compared to a low-dose. Conclusion: Currently available totality of evidence reflects a possible causal association between ibuprofen and hypoglycemia that need to be substantiated with further studies.