The combined treatment with insulin and sulfonylurea in non-insulin-dependent diabetic patients with secondary failure. Rationale and guidelines.

We propose that combined therapy with insulin plus sulfonylurea can be a useful approach for the treatment of those patients with NIDDM who fail to respond to diet or therapy with OHA (secondary failure). The use of relatively small doses of insulin can correct hypoinsulinemia due to impairment of endogenous insulin secretion, reduce basal hepatic glucose production and lower fasting plasma glucose concentration. Reduction of glucose level in plasma can favor the action of sulfonylurea drugs which can both stimulate insulin secretion in response to the meal and, perhaps, improve peripheral insulin sensitivity. The permissive effect of sulfonylurea drugs on insulin action can also avoid the use of large pharmacological amounts of insulin and reduce the risk of related side effects such as hypoglycemia and weight gain. The overall amelioration of prevalent plasma glucose concentrations can avoid the toxic effect of hyperglycemia on the β cell and possibly on the peripheral tissues. Based on these considerations, in patients with NIDDM who do not respond to OHA one should start a combined treatment with insulin and sulfonylurea agents and evaluate its effect on metabolic control before shifting to the traditional program of insulin therapy.