Insulin Glargine

Abstract

Insulin glargine is a human insulin analogue prepared by recombinant DNA technology. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant in relation to conventional human insulins, with no pronounced peak over 24 hours. This allows once-daily administration as basal therapy. Early randomised trials with insulin glargine generally showed greater reductions in fasting blood or plasma glucose levels and a reduced frequency of nocturnal hypoglycaemia relative to neutral protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus. In addition to this basal therapy, patients continued to use the regular mealtime insulin regimen to which they were accustomed. More recent data with insulin glargine have included evidence of improved glycaemic control, with improvements in satisfaction with treatment over NPH insulin. Furthermore, the time of day at which insulin glargine is injected has no clinically relevant effect on glycaemic control in these patients. There are also data from small, nonblind studies to suggest comparable glycaemic control with insulin glargine and continuous subcutaneous insulin infusion. Results from comparative studies and meta-analyses in individuals with type 2 diabetes show lower incidences of nocturnal hypoglycaemia with insulin glargine than with NPH insulin, with two studies showing a significantly greater improvement in glycosylated haemoglobin levels with insulin glargine than with NPH. Insulin glargine is well tolerated, and is not associated with greater immunogenicity or increases in bodyweight than NPH insulin. Long-term data show maintenance of glycaemic control with insulin glargine for up to 39 months in adults and children with type 1 and adults with type 2 diabetes. In conclusion, insulin glargine is an effective and well tolerated basal insulin therapy when given as a single daily subcutaneous injection to patients with diabetes, with benefits in terms of glycaemic control and reduced frequency of hypoglycaemia over regimens based on conventional basal insulins. Accumulating data and official recommendations show the suitability of insulin glargine for first-line use in selected patients with type 2 diabetes who require insulin treatment, as well as in patients with type 1 disease, and confirm its use in children and adolescents.

The evolution of commercial drug delivery technologies

“…Drug modifications have been particularly important for the delivery of insulin. For example, long-acting formulations such as insulin glargine (Lantus), a modified human insulin with pH-dependent solubility that forms microprecipitates in the subcutaneous space, and degludec (Tresiba), an acylated insulin analogue that forms high-molecular-weight complexes, were made possible via rational modifications to the structure of insulin 129,130 . In these formulations, insulin monomers are slowly released from a subcutaneous depot, thus mimicking aspects of natural host-mediated insulin secretion, reducing injection frequency and the risk of hypoglycaemia and improving glycaemic control 131 .…”

Insulin glargine 300U/ml in the management of diabetes: clinical utility and patient perspectives

“…The insulin then slowly dissipates from these microprecipitates, allowing it to be absorbed into the circulation. 19 …”

Modern basal insulin analogs: An incomplete story

“…While there was no clear benefit during pre-approval data of glargine over NPH, subsequent post-FDA approval studies [ Table 3 ] and their meta-analysis [ Table 4 ] did show significant benefit of glargine over NPH based mainly on hypoglycemia outcome, especially nocturnal hypoglycemia. [ 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 ] Some studies also showed benefit in A1c and FBS reduction compared to NPH. Finally, a CV trial of glargine, Outcome Reduction with an Initial Galrgine Intervention (ORIGIN) trial showed CV neutrality of glargine over 6.2 years.…”