Minimizing Hypoglycemia in Diabetes Diabetes Care 2015;38:1583–1591 | DOI: 10.2337/dc15-0279 Hypoglycemia caused by treatment with a sulfonylurea, a glinide, or insulin coupled with compromised defenses against the resulting falling plasma glucose concentrations is a problem for many people with diabetes. It is often recurrent, causes significant morbidity and occasional mortality, limits maintenance of euglycemia, and impairs physiological and behavioral defenses against sub- sequent hypoglycemia. Minimizing hypoglycemia includes acknowledging the problem; considering each risk factor; and applying the principles of intensive glycemic therapy, including drug selection and selective application of diabetes treatment technologies. For diabetes health-care providers treating most people with diabetes who are at risk for or are suffering from iatrogenic hypoglycemia, these principles include selecting appropriate individualized glycemic goals and providing structured patient education to reduce the incidence of hypoglycemia. This is typically combined with short-term scrupulous avoidance of hypoglycemia, which often will reverse impaired awareness of hypoglycemia. Clearly, the risk of hypoglycemia is modifiable. Hypoglycemia is the major limiting factor in the glycemic management of diabetes with a sulfonylurea, a glinide, or insulin (1,2). It is often recurrent, causes significant morbidity in most people with type 1 diabetes and in many with advanced type 2 diabetes (i.e., those with absolute endogenous insulin deficiency), and is sometimes fatal. Hypoglycemia limits maintenance of euglycemia over a lifetime of diabetes and, thus, generally prevents full realization of the benefits of glycemic control. It impairs defenses against subsequent falling plasma glucose concentrations and can cause impaired awareness of hypoglycemia, therefore resulting in a vicious cycle of recurrent hypoglycemia. The problem of hypoglycemia in diabetes has been recently reviewed in detail (1,2). The intent of this article is not to reiterate that information but, rather, to summarize the relevant background and then focus on pragmatic approaches to minimizing hypoglycemia. Efforts to minimize hypoglycemia include acknowledging the problem, considering each risk factor, and applying the relevant principles of intensive glycemic therapy (3–6). The principles of intensive glycemic therapy in- clude avoiding sulfonylureas and glinides; using more physiological insulin regi- mens, such as insulin analogs, when insulin is indicated; ensuring users are confident in their self-management; considering insulin treatment technologies such as continuous subcutaneous insulin infusion (CSII), continuous glucose moni- toring (CGM), and CSII with CGM (ideally with suspension of insulin infusion when glucose levels fall to a selected low value) for selected patients; and closed-loop insulin or insulin and glucagon replacement or pancreas or pancreatic islet trans- plantation for the few patients in whom hypoglycemia persists. However, for the majority of people with diabetes who are at risk for or are suffering from iatrogenic hypoglycemia, the principles include selecting appropriate individualized glycemic Corresponding author: Philip E. Cryer, pcryer@ wustl.edu. Received 7 February 2015 and accepted 24 May 2015. *A complete list of the members of the Interna- tional Hypoglycaemia Study Group can be found in the APPENDIX. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. International Hypoglycaemia Study Group* Diabetes Care Volume 38, August 2015 1583 REVIEW