Hypoglycemic potential of current and emerging pharmacotherapies in type 2 diabetes mellitus

Intensive glycemic control can reduce the risk of microvascular complications in patients with type 2 diabetes mellitus (T2DM). However, hypoglycemia induced by diabetes medications is recognized as a major limiting factor in the attainment of glycemic goals. Mild hypoglycemia is relatively common in patients with T2DM, and the prevalence of severe hypoglycemia increases with insulin treatment and can approach the prevalence seen in patients with type 1 diabetes. Mild hypoglycemia and the fear of hypoglycemia can have a substantial impact on the physical, mental, social, and economic well-being of patients with T2DM. Severe hypoglycemia is more serious and may be associated with an increased risk of dementia, cardiovascular events, and death. Insulin and insulin secretagogue therapies (eg, sulfonylureas and meglitinides) are the major causes of hypoglycemia in patients with T2DM. Other diabetes drugs, such as metformin, when used as monotherapy, have a low risk of hypoglycemia. Emerging experimental therapies, such as activators of the free fatty acid receptor 1, G protein-coupled receptor 119 agonists, glucokinase activators, inhibitors of 11β-hydroxysteroid dehydrogenase type 1, and sodium-glucose co-transporter 2 inhibitors, some of which have mechanisms of action consistent with a potential low risk of hypoglycemia, may help patients with T2DM achieve improved glycemic control.