Insulin Glulisine: A Review of its Use in the Management of Diabetes Mellitus

Authors: Garnock-Jones, Karly P.; Plosker, Greg L.

Source: Drugs, Volume 69, Number 8, 4 June 2009 , pp. 1035-1057(23)

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Abstract:

Abstract Insulin glulisine (Apidra®) is a human insulin analogue approved for the improvement of glycaemic control in adults, adolescents and children with diabetes mellitus. It has similar binding properties, and is associated with a faster onset but similar level of glucose disposal, to regular human insulin (RHI). Insulin glulisine and insulin lispro have similar effects on glucose levels.

Insulin glulisine is effective when compared to other short- and rapid-acting insulins, demonstrating either noninferiority, no significant difference, or superiority in primary endpoints in studies involving patients with type 1 and type 2 diabetes. It is more effective and has a faster onset and shorter duration of activity than RHI. Insulin glulisine is as effective as insulin lispro in patients with type 1 diabetes; however, there is a need for further, well designed head-to-head comparisons with insulin lispro in patients with type 2 diabetes and with insulin aspart in patients with type 1 or type 2 diabetes to fully establish the place of insulin glulisine in the management of diabetes. Insulin glulisine has a flexible administration period, as it can be administered immediately before or after meals. Hypoglycaemia, a common risk with insulins, occurs at a similar rate among recipients of insulin glulisine to that seen with other insulins. Thus, insulin glulisine is an effective and well tolerated option for the treatment of patients with type 1 and type 2 diabetes.

Pharmacological Properties Human insulin was altered to form insulin glulisine by replacing asparagine with lysine at position B3 and lysine with glutamic acid at position B29. The majority of in vitro and in vivo studies have shown that the binding of insulin glulisine to the insulin receptor (to therapeutic effect) and to the insulin-like growth factor-1 receptor (to mitogenic effect) is similar to that of RHI.

Insulin glulisine is associated with a faster glucose-lowering effect than RHI, but shows a similar level of glucose disposal overall, in patients with type 1 or type 2 diabetes. Insulin glulisine and insulin lispro appear similar with regard to speed and extent of glucose lowering in patients with type 1 or type 2 diabetes. In clinical trials in patients with type 1 or type 2 diabetes, insulin glulisine was associated with preprandial blood glucose levels that were at least as low as comparator agents, and on occasion significantly lower than those seen with RHI or (with basal insulin glargine) premixed insulin. Body mass index (BMI) does not appear to have an effect on blood glucose control in volunteers.

The majority of clinical trials reported (where stated) no significant difference between insulin glulisine and comparator agents in terms of change in bodyweight. Insulin glulisine appears to be associated with a closer approximation of normal microvascular blood flow and endothelial function than RHI, and end-organ metabolic effects associated with the administration of insulin glulisine, insulin lispro and RHI appear to be similar.

Insulin glulisine appears to have a similar total systemic availability to RHI, but with faster absorption, in patients with type 1 and type 2 diabetes, whereas it does not differ from insulin lispro with regard to these parameters in these patient populations. Patients with type 1 and type 2 diabetes had a maximum serum insulin glulisine concentration (C_max) of 120 and 92 μU/mL, a time to C_max of 51 and 83 minutes, and an area under the insulin glulisine concentration-time curve from time zero to endpoint of 16 120 and 18 408 μU·min/mL. Timing of administration (with regard to meal) and injection site did not appear to have significant effects on pharmacokinetic parameters.

Insulin glulisine, administered by subcutaneous injection, has an approximate absolute bioavailability of 70% and is associated with low plasma protein binding. After intravenous administration, the volume of distribution and elimination of insulin glulisine appears to be similar to those of RHI, but after subcutaneous administration the elimination is more rapid than with RHI. Insulin glulisine has a total clearance of 927 mL/min after intravenous administration and its metabolism is unlikely to differ from that of RHI.

Age, BMI and ethnicity do not appear to have any effect on the pharmacokinetic parameters of insulin glulisine. A reduction in the dosage of insulin may be required in the presence of renal impairment.

Document Type: Research article

Affiliations: 1: Wolters Kluwer Health ∣ Adis, Auckland, New Zealand, an editorial office of Wolters Kluwer Health, Philadelphia, Pennsylvania, USA

Publication date: 2009-06-04

Insulin Glulisine: A Review of its Use in the Management of Diabetes Mellitus

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