Anti-glycation and anti-albuminuric effects of GLY-230 in human diabetes

Laurence Kennedy, Maria Pilar Solano, Luigi Meneghini, Margaret Lo, Margo P. Cohen

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Background/Aims: 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 (μg 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.

Original languageEnglish (US)
Pages (from-to)110-116
Number of pages7
JournalAmerican Journal of Nephrology
Volume31
Issue number2
DOIs
StatePublished - Feb 1 2010

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Keywords

  • Clinical studies
  • Diabetic nephropathy
  • Glycated albumin
  • Glycation inhibitor
  • Microalbuminuria

ASJC Scopus subject areas

  • Nephrology

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