Angiotensin-converting enzyme inhibitors used concomitantly with insulin secretagogues and the risk of serious hypoglycemia Journal Article


Authors: Hee Nam, Y.; Brensinger, C. M.; Bilker, W. B.; Flory, J. H.; Leonard, C. E.; Hennessy, S.
Article Title: Angiotensin-converting enzyme inhibitors used concomitantly with insulin secretagogues and the risk of serious hypoglycemia
Abstract: Serious hypoglycemia is a major adverse event associated with insulin secretagogues. Previous studies have suggested a potential relationship between angiotensin-converting enzyme inhibitors (ACEIs) used with sulfonylureas and serious hypoglycemia, and widely used drug compendia warn of this potential drug-drug interaction. We investigated the association between serious hypoglycemia and concomitant use of ACEIs in patients receiving insulin secretagogues, using the self-controlled case series design and Medicaid claims data from 5 US states linked to Medicare claims from 1999–2011. The exposure of interest was active prescription for ACEIs during insulin secretagogue or metformin (negative control object drug) episodes. The outcome was hospital presentation for serious hypoglycemia, identified by discharge diagnosis codes in inpatient and emergency department claims (positive predictive value ~ 78–89%). We calculated confounder-adjusted rate ratios (RRs) and 95% confidence internals (CIs) of outcome occurrence during ACEI-exposed vs. ACEI-unexposed time using conditional Poisson regression. The RRs for ACEIs were not statistically elevated during observation time of glipizide (RR, 1.06; CI, 0.98–1.15), glyburide (RR, 1.05; CI, 0.96–1.15), repaglinide (RR, 1.15; CI, 0.94–1.41), or metformin (RR, 1.02; CI, 0.97–1.06); but was modestly elevated with glimepiride (RR, 1.23; CI, 1.11–1.37) and modestly reduced with nateglinide (RR, 0.73; CI, 0.56–0.96). The overall pattern of results do not suggest that ACEIs used with insulin secretagogues were associated with increased rates of serious hypoglycemia, with the possible exception of glimepiride. © 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics
Journal Title: Clinical Pharmacology & Therapeutics
Volume: 111
Issue: 1
ISSN: 0009-9236
Publisher: Nature Publishing Group  
Date Published: 2022-01-01
Start Page: 218
End Page: 226
Language: English
DOI: 10.1002/cpt.2377
PUBMED: 34312836
PROVIDER: scopus
PMCID: PMC8678147
DOI/URL:
Notes: Article -- Export Date: 3 January 2022 -- Source: Scopus
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  1. James H Flory
    35 Flory