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.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hypoglycemia/chemically induced , Hypoglycemic Agents/adverse effects , Hypolipidemic Agents/adverse effects , Aged , Algorithms , Cohort Studies , Drug Interactions , Female , Fenofibrate/administration & dosage , Fenofibrate/adverse effects , Glipizide/administration & dosage , Glipizide/adverse effects , Glyburide/administration & dosage , Glyburide/adverse effects , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hypoglycemia/epidemiology , Hypoglycemic Agents/administration & dosage , Hypolipidemic Agents/administration & dosage , Incidence , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Sulfonylurea Compounds/administration & dosage , Sulfonylurea Compounds/adverse effectsABSTRACT
A drug-drug interaction (DDI) occurs when one or more drugs affect the pharmacokinetics (the body's effect on the drug) and/or pharmacodynamics (the drug's effect on the body) of one or more other drugs. Pharmacoepidemiologic studies are the principal way of studying the health effects of potential DDIs. This article discusses aspects of pharmacoepidemiologic research designs that are particularly salient to the design and interpretation of pharmacoepidemiologic studies of DDIs.
Subject(s)
Drug Interactions , Epidemiologic Research Design , Pharmacoepidemiology/methods , HumansABSTRACT
We conducted a population-based case-control study to assess the myocardial infarction (MI) and stroke risks associated with sulphonylureas and insulin when used in combination with metformin. Cases had type 2 diabetes and used metformin + insulin or metformin + sulphonylureas at the time of a first MI or first stroke between 1995 and 2010; controls used the same treatment combinations and were randomly sampled from the same population. MI and stroke diagnoses and potential confounders were validated by medical record reviews. Compared with metformin + sulphonylurea, metformin + insulin was associated with similar risks of MI or stroke [odds ratio 0.98 (95% confidence interval 0.63-1.52)]. Meta-analysis with another observational study improved the precision of the risk estimate [relative risk 0.92 (95% confidence interval 0.69-1.24)]. Current evidence suggests that there may not be large differences in cardiovascular risk associated with the use of insulin or sulphonylureas when used in combination with metformin.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Metformin/therapeutic use , Myocardial Infarction/prevention & control , Stroke/prevention & control , Sulfonylurea Compounds/therapeutic use , Aged , Case-Control Studies , Diabetes Mellitus, Type 2/complications , Diabetic Angiopathies/chemically induced , Diabetic Angiopathies/complications , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/prevention & control , Diabetic Cardiomyopathies/chemically induced , Diabetic Cardiomyopathies/complications , Diabetic Cardiomyopathies/epidemiology , Diabetic Cardiomyopathies/prevention & control , Drug Therapy, Combination/adverse effects , Female , Humans , Hypoglycemic Agents/adverse effects , Incidence , Insulin/adverse effects , Male , Medical Records , Metformin/adverse effects , Middle Aged , Myocardial Infarction/chemically induced , Myocardial Infarction/complications , Myocardial Infarction/epidemiology , Practice Guidelines as Topic , Proportional Hazards Models , Risk Factors , Stroke/chemically induced , Stroke/complications , Stroke/epidemiology , Sulfonylurea Compounds/adverse effects , Washington/epidemiologyABSTRACT
Demographic and clinical risk factors are important in guiding vaccination policy for pneumococcal pneumonia. We present data on these variables from a population-based surveillance network covering adult bacteraemic pneumococcal pneumonia (BPP) in the Delaware Valley region from 2002 to 2004. Surveillance data were used with U.S. Census data and a community health survey to calculate stratified incidence rates. Missing data were handled using multiple imputation. Overall rates of adult BPP were 10.6 cases/100 000 person-years. Elevated rates were seen in the elderly (>65 years), Native Americans, African Americans, the less-educated (less than high-school education), the poor, smokers, and individuals with histories of asthma, cancer, or diabetes. Multivariable modelling suggested that income was more robustly associated with risk than African American race. Of methodological interest, this association was not apparent if census block-group median income was used as a proxy for self-reported income. Further research on socioeconomic risk factors for BPP is needed.
