Insulin glargine

General information

Insulin glargine is a long-acting human insulin analogue, in which phenylalanine is removed from site 30 of the C terminal of the B chain and two arginine molecules replace it, adding two positive charges; asparagine on site 21 of the A chain is replaced by the more stable glycine to avoid deamination. Older long-acting insulins, such as protamine zinc insulin and insulin zinc suspension (crystalline) (ultralente), had a maximal hypoglycemic effect after about 20 hours (in the middle of the night), and the glucose-lowering action then abated gradually. The newer analogues have a more constant profile of action [ ].

The binding of insulin analogues to insulin and IGF-I receptors and their metabolic and mitogenic properties have been evaluated in vitro [ ]. In general the metabolic potencies correlated with insulin receptor binding and the mitogenic properties correlated with IGF-I receptor binding. The rapid-acting analogues resembled insulin, except that the binding of insulin lispro to the IGF-I receptor was slightly increased. Insulin glargine had a 6- to 8-fold greater affinity for IGF-I and mitogenic potency than human insulin (suggesting greater growth-stimulating potential). In insulin detemir the balance between the metabolic and mitogenic potency was not changed, but receptor affinity was reduced, which may explain its lower efficacy on a molar base in humans.

Insulin glargine has been reviewed [ ]. The general conclusion was that it is an effective long-acting insulin with no pronounced peaks of action. Patients using insulin glargine have a reduced risk of hypoglycemia. Insulin glargine, which is metabolically active for at least 24 hours, could have an overlapping effect after a second injection. However, there was no evidence of accumulation when insulin glargine, mean dose 24 U/day, was used in combination with insulin lispro for 11 days [ ]. In reaction to comments, and discussing whether fluctuations in insulin concentrations still occur during the administration of insulin glargine, the authors agreed that the dose should be constant for at least 2 days before a change is made. It is also not clear whether higher doses of insulin glargine could accumulate because of slower inactivation [ ].

Drug studies