Vanadium treatment of type 2 diabetes: A view to the future

3-Hydroxy-2-methyl-4-pryone and 2-ethyl 3-hydroxy-4-pyrone (maltol and ethyl maltol, respectively) have proven especially suitable a ligands for vanadyl tons, fit potential insulin enhancing agents for diabetes mellitus. Both bis(maltolato)oxovanadium(IV) (BMOV), and the ethylmaltol analog, bis(ethylmaltolato)oxovanadium(IV) (BEOV), have the desired intermediate stability for pro-drug use, and have undergone extensive pie-clinical testing for safety and efficacy. Pharmacokinetic evaluation indicates a pattern of biodistribution consistent with fairly rapid dissociation and uptake, binding to serum transferrin for systemic circulation and transport to tissues, with preferential uptake in bone. These bis-ligand oxovanadium(IV) (VOL2) compounds have a clear advantage over inorganic vanadyl sulfate in terms of bioavailability and pharmaceutical efficacy. BEOV has now completed Phase I and has advanced to Phase II clinical trials. In the Phase I trial, a ran-e of doses horn 10 mg, to 90 mg BEOV, given orally to non-diabetic volunteers, resulted in no adverse effects, all biochemical parameters remained within normal limits. In the Phase IIa trial, BEOV (AKP-020). 20 mg, daily for 28 clays, per os, in seven type 2 diabetic Subjects, was associated with reductions in fasting blood and glucose and %HbA1c; improved responses to oral glucose tolerance testing, versus, the observed worsening of diabetic symptoms in the two placebo controls. (C) 2009 Elsevier Inc. All rights reserved.