To estimate the prevalence of type 2 diabetes in Italy and to investigate patient-related variables associated with the use of different antihyperglycemic therapies. This study was conducted between the years 2000-2003 from a source population comprising a cumulative sample of 394,719 patients from 320 General Practitioners across Italy, who provide information to the Health Search/Thales Database (HSD). A total sample of 23,729 of patients with type 2 diabetes age 15 years or older was selected from the source population. During the study years, the prevalence of type 2 diabetes increased from 4.7 to 6.0%. A significant increase in the use of antihyperglycemic therapy was also observed between 2000 and 2003. In particular, the use of biguanides increased. During the same period, the use of sulfonylurea monotherapy, oral combination therapy and insulin with oral combination therapy decreased. The results from the multivariate analysis revealed that healthier patients were more likely to be prescribed biguanide and sulfonylurea monotherapy, whereas patients with more diabetes complications and poorer glycemic control were more likely to be prescribed oral combination therapy or insulin (monotherapy or combination therapy). In conclusion, the study results appear to suggest that the prescribing patterns of Italian GPs and the predictors of different antihyperglycemic drug use are consistent with recent scientific evidence.