Oral hypoglycemic agents, along with dietary modification and exercise encompass the mainstay of treatment in early stages of T2DM. Biguanides and thiazolidinediones are two major groups of hypoglycemic medications that while function via different pathways, mare both effective in short- and long-term glucose control. These medications diminish or delay long term micro- and macrovascular complications associated with T2DM although at different rates. Excessive insulin resistance accounts for a sustained increase in cardiovascular incidents in T2DM subjects. Given the shared pathway of insulin resistance/fetuin-A/OPG in atherosclerosis formation, it is conceivable that insulin sensitizing anti-diabetes medications are able to modify successive CAD risk via direct and indirect amelioration of insulin resistance/fetuin-A/OPG. The present study is therefore designed to investigate the effects of metformin and pioglitazone monotherapy on serum concentrations of fetuin-A and OPG in a group of Iranian adults with newly diagnosed T2DM.