Longacting insulins ultralente and insulin glargine

Long-acting insulins are used to provide a basal level of insulin. Ultralente insulin reaches a peak gradually (14-18 h after injection), with a duration of action of up to 24h. Similar to lente insulin, ultralente is a suspension of large, zinc-containing crystals that have been precipitated in an acetate buffer.

Insulin glargine (Lantus) contains two modifications of the human insulin molecule that change both the onset and duration of action. Two arginine residues are added to the carboxyl terminal end of the insulin B-chain, and glycine is substituted for asparagine at the end of the A-chain (position A21). The latter modification prevents deamidation and dimerization. Overall, these changes result in a stable molecule that is soluble at an acidic pH but insoluble at the neutral pH of subcutaneous tissues. When insulin glargine is injected subcutaneously, the acidic solution is neutralized. Microprecipitates of insulin glargine form in the subcutaneous tissue and are slowly absorbed over a period of up to 24 h, resulting in a nearly constant level of insulin throughout the day. Insulin glargine may be given at any time of day and has been shown to cause less nocturnal hypoglycemia when used at bedtime than NPH insulin. Insulin glargine cannot be mixed prior to injection with any other insulin or solution because this will alter its pH and affect its absorption profile.

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