title: Comparative effectiveness of incident oral antidiabetic drugs on kidney function.
abstract: Diabetes is a major cause of chronic kidney disease, and oral antidiabetic drugs are the mainstay of therapy for most patients with Type 2 diabetes. Here we evaluated their role on renal outcomes by using a national Veterans Administration database to assemble a retrospective cohort of 93,577 diabetic patients who filled an incident oral antidiabetic drug prescription for metformin, sulfonylurea, or rosiglitazone, and had an estimated glomerular filtration rate (eGFR) of 60 ml/min or better. The primary composite outcome was a persistent decline in eGFR from baseline of 25% or more (eGFR event) or a diagnosis of end-stage renal disease (ESRD). The secondary outcome was an eGFR event, ESRD, or death. Sensitivity analyses included using a more stringent definition of the eGFR event requiring an eGFR <60 ml/min per 1.73 m(2) in addition to the 25% or more decline; controlling for baseline proteinuria thereby restricting data to 15,065 patients; and not requiring persistent treatment with the initial oral antidiabetic drug. Compared to patients using metformin, sulfonylurea users had an increased risk for both the primary and the secondary outcome, each with an adjusted hazard ratio of 1.20. Results of sensitivity analyses were consistent with the main findings. The risk associated with rosiglitazone was similar to metformin for both outcomes. Thus, compared to metformin, oral antidiabetic drug treatment with sulfonylureas increased the risk of a decline in eGFR, ESRD, or death.
authors.affiliation: VA Tennessee Valley, Clinical Science Research and Development, Geriatric Research Education Clinical Center (GRECC), Department of Medicine, Nashville, TN, USA. Adriana.hung@vanderbilt.edu
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Hung
authors.forename: Christianne L
authors.initials: CL
authors.lastname: Roumie
authors.forename: Robert A
authors.initials: RA
authors.lastname: Greevy
authors.forename: Xulei
authors.initials: X
authors.lastname: Liu
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Grijalva
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Murff
authors.forename: T Alp
authors.initials: TA
authors.lastname: Ikizler
authors.forename: Marie R
authors.initials: MR
authors.lastname: Griffin
mesh_terms: D000284:Administration, Oral; D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000503:physiopathology; D012189:Retrospective Studies; D012307:Risk Factors; D000077154:Rosiglitazone; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin