Les thérapeutiques hypoglycémiantes en association avec l'insuline dans le diabète de type 2 : lesquelles sont souhaitables, facultatives ou peu conseillées ?

Management of insulin-requiring type 2 diabetic patients with insulin is generally more complex than expected. The difficulties are mainly due to the insulin-resistant state, which is commonly encountered in type 2 diabetes. For instance achievement of satisfactory glycemic control usually requires high insulin doses, the consequence being a progressive weight gain. In order to overwhelm such adverse clinical effects, the use of combined therapy with other hypoglycemic agents has been proposed. The review of the various trials indicates first that the efficacy of add-on therapies in terms of HbA1c follows a decreasing ordinal scale. Insulin sensitizers (metformin and glitazones) that exert their effect on basal hyperglycemia are more efficient than insulin secretagogues. Among the latter category of drugs, the insulin secretagogues that reduce basal hyperglycemia (sulfonylureas and glinides), result in better lowering effects on blood glucose than those acting on postprandial blood glucose (gliptins and GLP-1 analogs). These observations are not surprising since insulin-requiring patients have usually a poor residual insulin secretion with HbA1c levels above 8%. In such clinical and pathophysiological situations, the best option is to target basal rather than postprandial hyperglycemia. Among insulin sensitizers, metformin, which has a neutral or beneficial effect on body weight, should be preferentially prescribed since the use of glitazones is usually associated with substantial weight gain.