Benefits and Risks of Transfer from Oral Agents to Insulin in Type 2 Diabetes Mellitus

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Abstract
The treatment of type 2 diabetes mellitus remains controversial. Since most patients are overweight or obese, regimens based on dietary modification and increased physical exercise are logical and safe treatment approaches. However, the long term impact of these interventions is frequently disappointing and phar-macotherapy is therefore required in the majority of patients. Oral antidiabetic agents, principally the sulphonylureas and biguanides, are often only partially effective, even in combination. Insulin is the treatment of choice for certain clinical situations, for example, pregnancy. Often insulin will be a temporary measure. Safety considerations will also point to the preferential use of insulin in other circumstances, for example, in patients with pronounced renal impairment. In addition, a significant proportion of patients with type 2 diabetes mellitus will ultimately require insulin therapy in the long term because of failure of oral agents to provide adequate glycaemic control (i.e. secondary failure). Reservations about insulin therapy in patients with type 2 diabetes mellitus, particularly elderly patients with cardiovascular complications, include hypoglycaemia and bodyweight gain. However, severe hypoglycaemia occurs with considerably lower frequency than in patients with type 1 diabetes mellitus. To date, no clear evidence has emerged implicating exogenous insulin therapy in the promotion of cardiovascular disease. On the contrary, recent clinical and experimental studies suggest anti-atherogenic effects. Insulin therapy can be successful in type 2 diabetes mellitus if patients are carefully selected. Twice daily isophane (neutral protamine Hagedorn; NPH) or pre-mixed insulin is used routinely in many centres. The role of combinations of insulin and oral agents remains an area of controversy. Combined therapy with sulphonylureas may be more expensive and clear clinical advantages have not been consistently demonstrated. Bodyweight gain may be lessened by the concomitant use of metformin and troglitazone may improve glycaemic control in obese patients. Procrastination about transfer to insulin is not uncommon. Patient acceptance may be facilitated by a positive attitude from the diabetes care team and discussion of the possibility at a relatively early stage. Adequate support from a multi-disciplinary team is important for safe and effective insulin therapy. Even so, in the long term, attainment of glycaemic targets may prove difficult to sustain with present therapeutic strategies.