Antidiabetic Activity

The primary activity of insulin, including Humalog, is the regulation of glucose metabolism. In addition, all insulins have several anabolic and anti-catabolic actions on many tissues in the body. In muscle and other tissues (except the brain), insulin causes rapid transport of glucose and amino acids intracellularly, promotes anabolism, and inhibits protein catabolism. In the liver, insulin promotes the uptake and storage of glucose in the form of glycogen, inhibits gluconeogenesis, and promotes the conversion of excess glucose into fat.

Humalog has been shown to be equipotent to human insulin on a molar basis. One unit of Humalog has the same glucose-lowering effect as one unit of human regular insulin, but its effect is more rapid and of shorter duration. The glucose-lowering activity of Humalog and human regular insulin is comparable when administered to normal volunteers by the intravenous route.

Pharmacokinetics

Absorption and Bioavailability

Humalog is as bioavailable as human regular insulin, with absolute bioavailability ranging between 55% to 77% with doses between 0.1 to 0.2 U/kg, inclusive. Studies in normal volunteers and patients with type 1 (insulin-dependent) diabetes demonstrated that Humalog is absorbed faster than human regular insulin (U-100) (see Figure 2). In normal volunteers given subcutaneous doses of Humalog ranging from 0.1 to 0.4 U/kg, peak serum levels were seen 30 to 90 minutes after dosing. When normal volunteers received equivalent doses of human regular insulin, peak insulin levels occurred between 50 to 120 minutes after dosing. Similar results were seen in patients with type 1 diabetes. The pharmacokinetic profiles of Humalog and human regular insulin are comparable to one another when administered to normal volunteers by the intravenous route. Humalog was absorbed at a consistently faster rate than human regular insulin in healthy male volunteers given 0.2 U/kg human regular insulin or Humalog at abdominal, deltoid, or femoral subcutaneous sites, the three sites often used by patients with diabetes. After abdominal administration of Humalog, serum drug levels are higher and the duration of action is slightly shorter than after deltoid or thigh administration (see DOSAGE AND ADMINISTRATION). Humalog has less intra- and inter-patient variability compared to human regular insulin.

Figure 2 : Serum Humalog and insulin levels after subcutaneous injection of human regular insulin or Humalog (0.2 U/kg) immediately before a high carbohydrate meal in 10 patients with type 1 diabetes.*

Distribution

The volume of distribution for Humalog is identical to that of human regular insulin, with a range of 0.26 to 0.36 L/kg.

Metabolism

Human metabolism studies have not been conducted. However, animal studies indicate that the metabolism of Humalog is identical to that of human regular insulin.

Elimination

When Humalog is given subcutaneously, its t½ is shorter than that of human regular insulin (1 vs. 1.5 hours, respectively). When given intravenously, Humalog and human regular insulin show identical dose-dependent elimination, with a t½ of 26 and 52 minutes at 0.1 U/kg and 0.2 U/kg, respectively.

Pharmacodynamics

Studies in normal volunteers and patients with diabetes demonstrated that Humalog has a more rapid onset of glucose-lowering activity, an earlier peak for glucose-lowering, and a shorter duration of glucose-lowering activity than human regular insulin (see Figure 3). The earlier onset of activity of Humalog is directly related to its more rapid rate of absorption. The time course of action of insulin and insulin analogs, such as Humalog, may vary considerably in different individuals or within the same individual. The parameters of Humalog activity (time of onset, peak time, and duration) as designated in Figure 3 should be considered only as general guidelines. The rate of insulin absorption and consequently the onset of activity is known to be affected by the site of injection, exercise, and other variables (see PRECAUTIONS, General).

Figure 3 : Blood glucose levels after subcutaneous injection of human regular insulin or Humalog (0.2 U/kg) immediately before a high carbohydrate meal in 10 patients with type 1 diabetes.*

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