Inability to achieve adequate glycaemic control with a logical combination of oral therapies is likely to indicate that the natural history of the disease has progressed to a state of severe beta cell failure.In this situation it is usually necessary to switch to insulin therapy.Similarly,failure to respond to an oral agent (so-called primary failure)or loss of control (secondary failure) usually reflects a severe degree of insulin deficiency and early need for insulin.All oral antidiabetic agents are contraindicated in thpe 1 diabetes and in major metabolic decompensation.Insulin may be required temporarily during intercurrent severe illness.