This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Murad, M. H. Articles by Montori, V. M. Search for Related Content PubMed PubMed Citation Articles by Murad, M. H. Articles by Montori, V. M. Related Collections Diabetes and Insulin Metabolism

Drug-Induced Hypoglycemia: A Systematic Review

Division of Preventive Medicine (M.H.M.), Knowledge and Encounter Research Unit (M.H.M., F.C.-Y., A.T.W., N.S., R.J.M., M.B.E., P.J.E., V.M.M.), and Department of Medicine (M.H.M., A.T.W., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905; Hospital Nacional de Geriatria y Gerontologia (F.C.-Y.), Caja Costarricense Seguro Social, San José, Costa Rica; and Division of Endocrinology (V.M.M.), Diabetes, Metabolism, Nutrition, Mayo Clinic, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Victor M. Montori, M.D., M.Sc., Mayo Clinic, W18A, 200 First Street SW, Rochester, Minnesota 55905. E-mail: montori.victor{at}mayo.edu.

Context: Drug-induced hypoglycemia is a significant adverse effect that may cause important morbidity.

Objective: The aim of the study was to systematically review the literature for drugs reported to cause hypoglycemia and assess the quality of evidence and strength of association supporting this causal link.

Data Sources: We searched electronic databases (MEDLINE, EMBASE, Web of Science, and SCOPUS) and the drug information system Micromedex through November 2007 and sought additional references from experts.

Study Selection: Studies were eligible if they reported hypoglycemia as a side effect of a drug not used to treat hyperglycemia, regardless of their design, language, size, or follow-up duration. We excluded hypoglycemia caused by industrial exposures, nonpharmacological chemical exposures, alcohol, herbs, nutritional supplements, and in vitro and animal studies.

Data Extraction: Reviewers extracted study characteristics and methodological quality and, when possible, data to estimate the odds of developing hypoglycemia when exposed to the offending agent.

Data Synthesis: We found 448 eligible studies that described 2696 cases of hypoglycemia associated with 164 different drugs. The quality of evidence supporting associations between drugs and hypoglycemia was mostly very low due to methodological limitations and imprecision. The most commonly reported offending drugs were quinolones, pentamidine, quinine, beta blockers, angiotensin-converting enzyme agents, and IGF.

Conclusions: Very low quality evidence substantiates the association between hypoglycemia and the use of numerous nondiabetic drugs.