Insulin glargine

Abstract

Based on the as yet small amount of data from full clinical study reports in peer-reviewed publications, insulin glargine appears to be a well-tolerated and effective basal insulin preparation for patients with type 1 or type 2 diabetes (including pediatric patients). Its delayed onset of action and prolonged, flat time-action profile mimic the action of endogenous basal insulin (or an insulin pump), decreasing the risk of hypoglycemic episodes. Insulin glargine may be a useful new option for meeting overnight insulin requirements, although most patients will require a rapid-acting insulin such as insulin lispro with or before meals for optimal management of blood glucose levels.

Supramolecular Protein Engineering

“…The principle of isoelectric precipitation underlies the prolonged action of insulin glargine, an analog in broad clinical use (Lantus) (11,12,30). Although slow release of zinc-free monomers enables basal metabolic regulation, concerns have been raised regarding IGF-1R-mediated mitogenicity (14) and possible dose-dependent cancer risk (15,16).…”

“…More rapid acting analogs are designed to limit self-assembly (8) or accelerate disassembly (9). Longer acting analogs are designed to promote self-assembly in the subcutaneous depot (10) or retard disassembly (11,12). These classes each exploit an inverse relationship between the size of a subcutaneous protein complex and rate of capillary absorption (8,9,12).…”

“…Its B-chain is extended by paired Arg residues (Fig. 1A, top, red) whose positively charged side chains shift the pI from 5.8 to 7.0 (11,12). Lantus is formulated at pH 4 as a clear unbuffered solution that, following subcutaneous injection, undergoes pH-dependent precipitation to form a slow release depot (11).…”

“…1A, top, red) whose positively charged side chains shift the pI from 5.8 to 7.0 (11,12). Lantus is formulated at pH 4 as a clear unbuffered solution that, following subcutaneous injection, undergoes pH-dependent precipitation to form a slow release depot (11). Insulin glargine exhibits increased cross-binding to the type 1 insulin-like growth factor receptor (IGF-1R), 3 a homolog of the insulin receptor (IR) (12,14).…”

Insulin Glargine in the intensive care unit: A model-based clinical trial design

“…It is administered subcutaneously and released very slowly into the blood plasma over 22 -26 hours [12]. Hence, it has potential advantages for a low intensity AGC protocol requiring only one daily administration.…”