A Review of the Structure, Pharmacokinetics, Pharmacodynamics, Efficacy and Safety of Insulin Glulisine in the Management of Diabetes Mellitus

Abstract

Glulisine (ApidraTM) is a rapid acting recombinant insulin analogue which differs from regular human insulin (RHI) by the substitution of lysine for asparagine at position B3 and glutamic acid for lysine at position B29. The chemical name is 3B-Lys-29- B-Glu-human insulin. The amino acid substitutions of glulisine and other rapid acting insulin analogues promote monomer stability, allowing for rapid dissociation and absorption after subcutaneous injection. It has a favourable pharmacokinetic and pharmacodynamic profile when compared with RHI, characterised by quicker absorption and a greater early disposal of glucose, thus replicating a more physiological response to a meal. It has been demonstrated to be superior to RHI in patients with Type 1 diabetes mellitus (DM) and at least non-inferior in the management of Type 2 DM with respect to reducing HbA1c and post-prandial glucose excursions, with a comparable safety profile. In efficacy trials comparing glulisine with lispro in patients with type 1 DM, glulisine was non-inferior with no significant difference in change in HbA1c or post-prandial glucose levels. However, although glulisine and lispro have been demonstrated to induce comparable total glucose disposals in normal subjects, glulisine causes earlier glucose disposal in both lean and obese subjects, has significantly faster subcutaneous absorption along with similar rates of adverse events, hypoglycemia and weight gain. There are limited data comparing the pharmacokinetics, pharmacodynamics, efficacy and safety of glulisine and aspart insulins.