The goal of sulphonylurea (S) treatment in Non-Insulin-Dependent Diabetes Mellitus (NIDDM - type 2 diabetes) subjects should be to obtain a satisfactory glycemic control (fasting glycemic levels < 140 mg%). The loss of an adequate blood glucose control after an initial variable period of S is known as secondary failure (SF). The number of SF are extremely variable among different trials for many reasons, some of which are patient-related: increased food intake, weight gain, non-compliance, poor physical activity, stress, diseases and÷or impaired pancreatic beta cell function, desensitization after S chronic therapy, reduced absorption, concomitant therapies. Many therapeutic strategies have been proposed to achieve an adequate metabolic control in type 2 diabetes patients: switch to intensive insulin therapy and subsequent return to S therapy; association with insulin; association with sulphonylureas plus biguanides. The association biguanides and S, in particular glibenclamide plus metformin, is now widely used by diabetologists in SF since glibenclamide improves insulin secretion while metformin exerts its antidiabetic.