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Traditional Insulin Compares Well Against Analogs

Newer long-acting insulin analogs are only marginally better at preventing nighttime hypoglycemia than traditional NPH insulin, found investigators here in a systematic review. Neither insulin glargine (Lantus) nor insulin detemir (Levemir) were superior to NPH (neutral protamine Hagedorn, or isophane) insulin at protecting against diabetes-related morbidity and mortality or improving quality of life, according to Karl Horvath, M.D., of the Medical University of Graz, and colleagues.

"Our analysis suggests, if at all, only a minor clinical benefit of treatment with long-acting insulin analogs for patients with diabetes mellitus type 2 treated with ‘basal’ insulin regarding symptomatic nocturnal hypoglycemic events," they reported in the second issue for 2007 of the Cochrane Library, which was published online.

"Until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir," the reviewers added.

"The review also shows that Lantus and Levemir had fewer problems with low blood sugar at night, giving greater security for those who experience this while sleeping," Dr. Buse added.

Dr. Horvath and colleagues conducted a systematic review of the literature comparing one or both of the long-acting analogs with insulin NPH to determine whether the newer agents could reduce the incidence of microvascular and macrovascular complications associated with hyperglycemia.

They collected studies from databases and from insulin manufacturers, focusing on randomized controlled studies with a minimum trial duration of 24 weeks. Two of the authors independently assessed the quality of each study and extracted data.
They identified six studies of mediocre quality (graded C by evidenced-based medicine standards) comparing insulin glargine to NPH insulin, and two studies comparing insulin detemir to NPH insulin. A total of 1,715 patients in the trials were randomized to insulin glargine, and 578 were assigned to receive insulin detemir. The trials lasted 24 to 52 weeks. The authors used metabolic control, measured by glycosylated hemoglobin as the main outcome measure.

"Our analysis of the currently available long-term trials comparing long acting insulin analogues with NPH insulin showed that insulin glargine and insulin detemir were almost identically effective compared to NPH insulin in long-term metabolic control (HbA1c)," they wrote.

There were no differences in overall episodes of severe hypoglycemia. The insulin analogs were, however, associated with significantly fewer nighttime hypoglycemic episodes than NPH insulin. In terms of other complications of therapy, one study found that insulin glargine was associated with a higher rate of progression of diabetic retinopathy, while a different study found the opposite to be true.

"Until long-term data on benefit and risk are available, we suggest a cautious approach to treatment with insulin glargine or insulin detemir," the authors wrote.

Practice Pearls:  Explain to patients who ask that insulin NPH and the newer insulin analogs insulin glargine and insulin determir are long-acting insulins designed to provide maintenance of basal glucose levels over longer periods, such as overnight, and that all three appear to perform the task well

Horvath K et al. "Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus (Review)." Cochrane Database of Systematic Reviews 2007, Issue 2.

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