General Information

Traditional regular human insulin requires people to inject their insulin dosage 30 minutes before eating. NovoLog has faster absorption, faster onset of action and shorter duration of action than regular human insulin. The quick onset of blood sugar lowering after injection of NovoLog allows people with diabetes to inject themselves immediately before eating, offering flexibility to patients.

Clinical Results

The six-month, open-label trial randomized 884 patients with type I diabetes to receive either human insulin thirty minutes before meals or NovoLog immediately before meals. Study results were presented at the American Diabetes Association annual meeting in San Diego on June 22.

Prior to randomization, all subjects received a four-week treatment regimen consisting of human insulin before meals and NPH insulin as basal insulin. HbA1c levels and eight-point daily blood glucose profiles were assessed at six months to evaluate efficacy.

At six months, HbA1c was significantly lower (p=0.005) in the insulin aspart group (7.8% ± 0.1) than the human insulin group (7.9% ± 0.2).

Blood glucose levels also showed superior reduction at six months in the insulin aspart group after breakfast, lunch and dinner, and before lunch (156 ± 3, 137 ± 3, 153 ± 3, and 126 ± 3 mg/dL, respectively) when compared to the human insulin group (185 ± 5, 162 ± 4, 168 ± 4, and 138 ± 4 mg/dL). The p-value for all comparisons was less than 0.016.

In addition, the prandial blood glucose increments -- defined as the mean of the differences between the blood glucose value 90 minutes after the meal and the blood glucose value just before the meal -- were significantly lower (p = 0.0001) in the NovoLog group (2.2 ± 2.2 mg/dL) than the human insulin group (28.4 ± 2.9 mg/dL), the investigators said.

The safety profiles for the two products were similar, with low frequencies of hypoglycemic episodes reported for both treatments. While the overall risk of hypoglycemia was similar, the authors noted that a smaller percentage of episodes occurred between midnight and 6 a.m. in the NovoLog group (16% of episodes vs. 34%). (from fdcreports.com)

Side Effects

Hypoglycemia and hypokalemia, as well as lipodystrophy and hypersensitivity, are among the potential clinical adverse effects associated with the use of all insulins.

Clinical trials comparing NovoLog with regular human insulin did not demonstrate a difference in adverse reaction frequency.

In controlled clinical trials, small, but evident elevations in alkaline phosphatase were observed in some patients that were treated with NovoLog. The clinical significance of this finding is unknown at this time.

Mechanism of Action

The main function of NovoLog is the regulation of glucose metabolism. Insulins bind to insulin receptors on both muscle and fat cells and then lower blood glucose by facilitating the cellular uptake of glucose and simultaneously preventing or slowing the output of glucose from the liver.

In standard mice and rabbit testing, one unit of NovoLog has the same glucose-lowering effect as one unit of regular human insulin. In humans, the effect is more rapid and shorter in duration than regular human insulin, due to NovoLog's faster absorption rate after injection.

Additional Information

As will all insulin preparations, the time course of NovoLog action may vary in different individuals or at different times in the same individual and is dependent on blood supply, injection site, temperature, and physical activity.

NovoLog is sold as NovoRapid outside the US. Novo Nordisk received marketing approval for NovoRapid from the European Union last year, and it is now available in several European countries, such as the United Kingdom and Germany. Other diabetes products currently in development include premixed and long-acting insulin analogues.