Antidiabetic agents in subjects with mild dysglycaemia: prevention or early treatment of type 2 diabetes?

Besides lifestyle, various pharmacological treatments have proven their efficacy to reduce the incidence of type 2 diabetes in high-risk individuals, especially in those with impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG). Major placebo-controlled clinical trials demonstrated favourable effects of various glucose-lowering drugs generally used for the treatment of type 2 diabetes, i.e. metformin, acarbose and thiazolidinediones (glitazones). These trials showed a lower rate of progression to overt diabetes and a higher regression rate to a normal glucose status with active treatment as compared to placebo after a follow up of several years. Ongoing trials should confirm such a favourable effect with those drugs and may demonstrate a similar protective effect with other pharmacological approaches such as glinides or even basal insulin regimen. However, the reported favourable effects were generally observed while the subjects were still on treatment, and partially vanished after a rather short period of wash-out of several weeks. Therefore, the distinction between a true preventing effect and simply a masking effect is difficult with glucose-lowering drugs. In addition, as type 2 diabetes is a progressive disease, it is still questionable whether the effect corresponds to a prevention effect or only to a postponing of the development of the disease. Owing to the pathophysiology of the disease, the only way to block the progression of type 2 diabetes is probably to avoid the progressive loss of beta-cell function and/or mass. Whatsoever, these data obtained in large clinical trials bring further argument to support early treatment of diabetes, even at a prediabetic state, in order to stop the vicious circle leading to an inevitable deterioration of glycaemia in predisposed subjects.