Effects of current therapeutic interventions on insulin resistance

Summary Summary. Although diet and exercise remain the cornerstones of type 2 diabetes therapy, attempts at lifestyle changes seldom result in the achievement of glycaemic control. As a result, the addition of pharmacological agents is usually necessary. Currently available treatment options improve glycaemic control in the short term; however, maintaining long‐term glycaemic control, halting disease progression, and preventing the complications of type 2 diabetes have all proven to be elusive therapeutic goals. For more than 30 years, sulphonylureas (SUs) have been first‐line therapy for the management of type 2 diabetes. These compounds control hyperglycaemia by stimulating insulin release from pancreatic β cells, and thus their benefits are limited to patients with preserved β‐cell function. Despite historic reliance on these agents to treat type 2 diabetes, long‐term use of SUs may desensitize β cells. The meglitinides (e.g. repaglinide) are a new class of non‐sulphonylurea secretagogues that bind to a different receptor on the β cell. Repaglinide has a short duration of action and may be useful for the treatment of postprandial hyperglycaemia. The biguanides (e.g. metformin) represent another class of antidiabetic agents and improve glycaemic control primarily by decreasing hepatic glucose output. Metformin and SUs provide similar glucose‐lowering effects, and, in combination, may provide additional benefits in some patients. Reducing the rate of glucose absorption with α‐glucosidase inhibitors (e.g. acarbose) has been explored as an alternative approach to the management of postprandial hyperglycaemia, but these agents do not address the primary defect in type 2 diabetes. Eventually, prolonged overproduction of insulin to compensate for hyperglycaemia leads to dramatically reduced β‐cell function, and exogenous insulin therapy is required.