Issue 163 Item 14 Glargine In Morning or Evening?

New study shows less nocturnal lows and better control in Type 2’s who take in morning.

Morning insulin glargine appears to lower the risk of nocturnal hypoglycemia in type 2 diabetics who take the sulfonylurea drug glimepiride, compared with bedtime insulin glargine or bedtime NPH insulin.

Therapy with oral antidiabetic drugs and bedtime neutral protamine Hagedorn (NPH) insulin is as effective as other, more complex insulin regimens and is associated with less weight gain. However, NPH insulin exhibits a peak of action 4 to 6 hours after injection and is associated with an increased risk of nocturnal hypoglycemia.

By comparison, insulin glargine, a newer human insulin analogue, exhibits a 24-hour action profile and may be more effective in achieving glycemic control compared to NPH when combined with oral antidiabetic drugs.

In their study, Andreas Fritsche, MD, with the Eberhard-Karls-Universitat, Tubingen, Germany, and colleagues conducted an open-label, randomized, controlled trial of 695 patients with type 2 diabetes whose diabetes was poorly controlled with oral antidiabetic drugs alone. Patients were randomized to treatment with morning insulin glargine, bedtime NPH insulin, or bedtime insulin glargine for 24 weeks in addition to 3 mg of glimepiride.

Hemoglobin A(1c) improvement was more pronounced with morning insulin glargine than with NPH insulin (p = 0.001) or bedtime insulin glargine (p = 0.008). Hemoglobin A(1c) levels improved by -1.24% with morning insulin glargine, -0.96% with bedtime insulin glargine, and by -0.84% with bedtime NPH insulin.

Improvement in baseline to end-point fasting blood glucose levels was similar in all three groups, the researchers found. However, patients receiving morning insulin glargine experienced the least nocturnal hypoglycemia (17% with morning insulin glargine versus 23% with bedtime insulin glargine and 38% with NPH insulin, p < 0.001).

"Insulin glargine injected in the morning resulted in better glycemic control than did bedtime NPH insulin, " the researchers conclude. "This can be explained by the longer action profile of insulin glargine and, therefore, better 24-hour glycemic control."

However, the finding that insulin glargine results in better glycemic control only when given in the morning was "unexpected and is not easy to explain," they point out. They speculate that the reason for the better glycemic control with morning insulin glargine is that the glucose-lowering effect of insulin glargine given in the morning together with glimepiride might be higher during the first 12 hours after insulin glargine injection. Ann Intern Med 2003;138:12:952-959