For glucose-lowering drugs inducing hypoglycemia, a marginally protective effect on the risk of MACE was observed for HbA1c 48-58 mmol/mol, whereas a significant reduction of microvascular complications was observed for HbA1c<49 mmol/mol, but with higher risk of severe hypoglycaemia. Drugs not inducing hypoglycaemia were associated with a reduction of MACE, renal adverse events, and all-cause mortality, for HbA1c<7% (no data for lower targets). Conclusions: the present paper illustrates the recommendations of the Italian guidelines for the treatment of type 2 diabetes on therapeutic targets for HbA1c. In synthesis, the improvement of glycemic control with drugs not inducing hypoglycemia is associated with a reduction in the risk of long-term chronic vascular and renal complications, and all-cause mortality suggesting an HbA1c target of 53 mmol/mol. When the reduction of HbA1c is achieved with drugs inducing hypoglycemia, a progressive reduction of complications and an increase in the risk of severe hypoglycemia is observed suggesting higher HbA1c thresholds (49-58 mmol/mol).