An overview of the rationale for pharmacological strategies in type 2 diabetes: from the evidence to new perspectives.

Therapeutic strategies in type 2 diabetic patients should not only integrate both the targets and indications of the different therapies but should be also a compromise between the patient's and physician's goals and willingnesses. The rationale for therapeutic targets is based on recommendations that differ from one country to another. Even though HbA1c remains the "gold standard", monitoring of blood glucose at fasting and postprandial time-points is a complementary tool for estimating both the quality and safety of diabetic control. Despite the lack of available strong evidence-based data it seems that achieving glucose levels < 130 mg/dl at fasting and < 180 mg/dl or < 140 mg/dl over postbreakfast or postlunch periods, respectively, might be a reasonable goal in most countries. The choice of appropriate strategies for treating type 2 diabetic patients should ideally be based on pathophysiological considerations. However for practical reasons, decisions for initiating or completing antidiabetic treatments are usually made by using such simple parameters as HbA1c and plasma glucose levels. The bridge between pathophysiological and clinical rationales can be obtained from the analysis of the relative contributions of fasting and postprandial glucose to the overall hyperglycaemia. In patients with HbA1c < 7.3%, postprandial glucose makes the major contribution to the overall hyperglycaemia, whereas the contribution of fasting glucose becomes progressively predominant in patients with HbA1c > 7.3%. As a consequence of these observations, initiation of antidiabetic treatments or implementation of second-line therapies should be aimed at reducing either postprandial excursions or fasting hyperglycaemia according to whether HbA1c levels are found respectively below or above a cut-off value of 7.3%.