Anti-glycation and anti-albuminuric effects of GLY-230 in human diabetes.
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.
Kennedy
Laurence
L
University of Florida, Gainesville, FL, USA.
Solano
Maria Pilar
MP
Meneghini
Luigi
L
Lo
Margaret
M
Cohen
Margo P
MP
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
C518289:2-(3-chlorophenylamino)phenylacetic acid; D000418:Albumins; D010919:Placebos; D004008:Diclofenac