title: Severe hypoglycemia in users of sulfonylurea antidiabetic agents and antihyperlipidemics.
abstract: Drug-drug interactions causing severe hypoglycemia due to antidiabetic drugs is a major clinical and public health problem. We assessed whether sulfonylurea use with a statin or fibrate was associated with severe hypoglycemia. We conducted cohort studies of users of glyburide, glipizide, and glimepiride plus a statin or fibrate within a Medicaid population. The outcome was a validated, diagnosis-based algorithm for severe hypoglycemia. Among 592,872 persons newly exposed to a sulfonylurea+antihyperlipidemic, the incidence of severe hypoglycemia was 5.8/100 person-years. Adjusted hazard ratios (HRs) for sulfonylurea+statins were consistent with no association. Most overall HRs for sulfonylurea+fibrate were elevated, with sulfonylurea-specific adjusted HRs as large as 1.50 (95% confidence interval (CI): 1.24-1.81) for glyburide+gemfibrozil, 1.37 (95% CI: 1.11-1.69) for glipizide+gemfibrozil, and 1.63 (95% CI: 1.29-2.06) for glimepiride+fenofibrate. Concomitant therapy with a sulfonylurea and fibrate is associated with an often delayed increased rate of severe hypoglycemia.
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Leonard
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: W B
authors.initials: WB
authors.lastname: Bilker
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Brensinger
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: X
authors.initials: X
authors.lastname: Han
authors.affiliation: Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Healthcare Policy and Research, Division of Comparative Effectiveness, Weill Cornell Medical College, New York, New York, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Flory
authors.affiliation: Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Flockhart
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Gagne
authors.affiliation: Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cardillo
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hennessy
mesh_terms: D000368:Aged; D000465:Algorithms; D015331:Cohort Studies; D004347:Drug Interactions; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage / Q000009:adverse effects; D005913:Glipizide / Q000008:administration & dosage / Q000009:adverse effects; D005905:Glyburide / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D007003:Hypoglycemia / Q000139:chemically induced* / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D013453:Sulfonylurea Compounds; C057619:glimepiride; D005905:Glyburide; D011345:Fenofibrate; D005913:Glipizide