Reducing the risk of iatrogenic hypoglycemia, while attempting to keep plasma glucose levels as close to the nondiabetic range as can be done safely, involves four steps (3,14). First, we need to address the issue of hypoglycemia in every patient contact. Then, if hypoglycemia is a problem, as is often the case, the next step is to review the extent to which the principles of aggressive glycemic therapy - patient education and empowerment, frequent SMBG, flexible drug regimens, individualized glycemic goals and ongoing professional guidance and support - are being applied. Next, we need to consider both the conventional risk factors - and adjust the drug regimen appropriately in relation to the meal and exercise plan, alcohol and other drug interactions and altered insulin sensitivity or clearance - and the risk factors that imply compromised glucose counterregulation. A history of severe hypoglycemia generally requires a substantive change in the regimen. With a history of hypoglycemia unawareness a 2-3 week period of scrupulous avoidance of hypoglycemia is indicated (10-12).

Treatment of a hypoglycemic episode is accomplished by carbohydrate ingestion (15-20g initially) if that is practical. If not, glucose can be given intravenously (25g initially) or glucagon (1.0 mg in adults) can be given subcutaneously, intramuscularly or intravenously. Parenteral treatments should be followed by oral feedings; glucose infusion is often required in sulfonylurea induced hypoglycemia. Prevention of hypoglycemia includes risk factor reduction and regimen adjustments as noted above. Among the sulfonylureas, there is some evidence that glimepiride causes less hypoglycemia than glyburide or glipizide. The insulin secretagogues repaglinide and nateglinide can cause hypoglycemia. Monotherapy with metformin, a thiazolidinedione, an α-glucosidase inhibitor a or GLP-1 agonist should not. In a basal-bolus insulin regimen the use of analogues (e.g., glargine or detemir as the basal insulin and lispro or aspart as the prandial insulin) reduces nocturnal hypoglycemia. In theory, continuous subcutaneous insulin infusion should be even safer in this regard. Nocturnal hypoglycemia is a common problem. Conventional bedtime snacks often do not last throughout the night. Experimental approaches include bedtime administration of the epinephrine simulating β2-adrenergic agonist terbutaline, the glucagon stimulating amino acid alanine or the slowly digested uncooked cornstarch.