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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.

SUBMITTER: Leonard CE

PROVIDER: S-EPMC4828264 | biostudies-other | 2016 May

REPOSITORIES: biostudies-other

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Severe hypoglycemia in users of sulfonylurea antidiabetic agents and antihyperlipidemics.

Leonard C E CE Bilker W B WB Brensinger C M CM Han X X Flory J H JH Flockhart D A DA Gagne J J JJ Cardillo S S Hennessy S S

Clinical pharmacology and therapeutics 20160117 5

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+antihy ...[more]

PMID: 26566262

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Project description:BackgroundTigecycline, the first glycylcycline-class drug, is a broad-spectrum antibiotic with activity against multi-drug resistant (MDR) organisms. We describe a case of sustained and severe hypoglycemia in a patient treated with tigecycline for pneumonia due to MDR Klebsiella pneumoniae.Case presentationA 74-year-old man was admitted for treatment of pneumonia. At admission he had prediabetes. In the hospital he developed renal failure. On day 3, the patient experienced severe shortness of breath. He was intubated and transferred to the intensive care unit (ICU) for ventilator support. In the ICU the antibiotic regimen was cefoperazone and sulbactam (1?g every 12?h). Continuous Renal Replacement Therapy was started on that day. Test for anti-neutrophil cytoplasmic antibodies (ANCA) was positive, and so the nephrologist and rheumatologist agreed on a diagnosis of ANCA-associated vasculitis, with renal and pulmonary involvement and acute renal failure. Plasmapheresis, and high-dose methylprednisolone treatment were started on day 6, and there was obvious improvement in the patient's condition. The steroid regimen was gradually tapered to oral prednisone (35?mg every day) on day 19. Afterwards, the patient's pneumonia worsened. Sputum culture showed Klebsiella pneumoniae sensitive to only tigecycline. Tigecycline treatment (100?mg every 12?h) was administered on day 20. Hypoglycemia started about 37?h after the first dose of tigecycline. Infusion of 50% glucose through the femoral vein was required for over 20?h to maintain normal blood glucose concentrations. Tigecycline was stopped, but the hypoglycemia resolved only after a further 34?h. The insulin and C-peptide levels were found to be markedly elevated during the hypoglycemia. The Naranjo scale score of 7 indicated that the likelihood of tigecycline causing severe hypoglycemia was "probable."ConclusionThis is the first report of sustained severe hypoglycemia due to tigecycline. Oversecretion of insulin appears to have been the cause of the hypoglycemia in our patient. The mechanism needs to be investigated.

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Severe hypoglycemia in users of sulfonylurea antidiabetic agents and antihyperlipidemics.

Publications

Severe hypoglycemia in users of sulfonylurea antidiabetic agents and antihyperlipidemics.

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