title: Anti-glycation and anti-albuminuric effects of GLY-230 in human diabetes.
abstract: OBJECTIVE
  Inhibiting nonenzymatic glycation with GLY-230 lowers glycated albumin without affecting hyperglycemia and ameliorates renal dysfunction in the db/db mouse, but the effects of this compound in man have not been assessed. We report results from the first clinical trial in patients with diabetes of this new glycation inhibitor.
  
  
  METHODS
  21 diabetic men were randomly assigned to receive a total dose of 250, 500 or 750 mg of GLY-230 or placebo (1:1:1:1.2 ratio) daily for 14 days to evaluate safety and the effect of drug on plasma concentrations of glycated albumin and on urinary albumin.
  
  
  RESULTS
  GLY-230 dose-responsively decreased glycated albumin in all participants, in whom HbA1c did not change. Among participants exhibiting microalbuminuria at baseline, mean albumin excretion significantly decreased in patients receiving GLY-230 (microg albumin/mg creatinine = 61.4 +/- 15.8 and 29.8 +/- 10.4 at baseline and completion, respectively; p = 0.001), but not placebo. There were no serious adverse events or laboratory abnormalities, and all safety parameters remained within normal limits.
  
  
  CONCLUSIONS
  This first-in-diabetic man study indicates that GLY-230 lowers glycated albumin and that this decrease is associated with a reduction in urine albumin excretion in patients with preexisting microalbuminuria. These data encourage further evaluation of GLY-230 in diabetic renal dysfunction.
authors.affiliation: University of Florida, Gainesville, FL, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Kennedy
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Solano
authors.forename: Luigi
authors.initials: L
authors.lastname: Meneghini
authors.forename: Margaret
authors.initials: M
authors.lastname: Lo
authors.forename: Margo P
authors.initials: MP
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000418:Albumins / Q000378:metabolism; D000419:Albuminuria / Q000150:complications / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D048909:Diabetes Complications / Q000188:drug therapy; D003920:Diabetes Mellitus / Q000188:drug therapy*; D004008:Diclofenac / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006031:Glycosylation; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology; D007668:Kidney / Q000378:metabolism; D008297:Male; D010919:Placebos; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: C518289:2-(3-chlorophenylamino)phenylacetic acid; D000418:Albumins; D010919:Placebos; D004008:Diclofenac