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J Clin Endocrinol Metab. 2012 May;97(5):1405-13. doi: 10.1210/jc.2011-2202. Epub 2012 Mar 22.

Update on insulin therapy for type 2 diabetes.

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Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.


Type 2 diabetes is characterized by insulin resistance and impaired insulin secretion at diagnosis and by progressive β-cell dysfunction over time. Insulin therapy is thus frequently required during the course of the disease to maintain glycemic control and prevent diabetes complications. Insulin should be initiated when alternative antihyperglycemic agents have failed or when symptomatic or marked hyperglycemia is present. Recent studies demonstrate that the addition of basal, prandial, basal/bolus, or premixed insulins to existing antihyperglycemic regimens effectively lowers glycosylated hemoglobin (HbA(1c)). The long-acting insulin analogs cause less nocturnal hypoglycemia than bedtime NPH, with comparable HbA(1c) reductions. Insulin detemir confers a weight advantage over glargine or NPH. Rapid-acting insulin analogs control postprandial hyperglycemia more effectively than regular insulin and modestly lower HbA(1c). For selected patients with severe insulin resistance, U-500 is a less expensive and potentially more effective alternative to U-100 insulin. Adverse effects of insulin, including weight gain and hypoglycemia, can be minimized by initial use of basal insulins in combination with metformin, incretin mimetics, or dipeptidyl-peptidase-IV inhibitors. Although in vitro studies suggest that hyperinsulinemia may promote tumorigenesis, no currently available insulin has been shown to increase cancer rates. Targeting near-normal glucose levels in insulin-treated patients should be reserved for those of younger age with a longer life expectancy, a shorter duration of diabetes, and little or no end-organ complications. A higher HbA(1c) target of 7-8% is more appropriate for patients less likely to benefit from intensive control and in those at high risk for severe hypoglycemia.

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