25.8: Insulin Formulations: Types and Delivery

Insulin preparations are categorized by their duration of action into short-acting and long-acting types. Two strategies are used to modify insulin's absorption and pharmacokinetic profile: slowing the absorption post-subcutaneous injection, or altering human insulin's amino acid sequence or protein structure. These changes retain the insulin's ability to bind to the insulin receptor, but alter its behavior in solution or after injection.

Short-acting insulins are divided into rapid-acting insulins (aspart, glulisine, lispro) and regular insulin. Regular insulin forms hexamers in neutral pH aqueous solutions, slowing absorption post-injection. In contrast, short-acting insulin analogs are absorbed more rapidly from subcutaneous sites, have lower hypoglycemia rates, and slightly improved A1c levels compared to regular insulin. They should be injected 15 minutes or less before a meal.

Long-acting insulins, such as NPH insulin (an intermediate-acting form) and insulin glargine, among others, are essential for managing diabetes. NPH insulin, a complex of native insulin with zinc and protamine, dissolves gradually post-injection, extending its action duration. It is typically administered once or twice daily with short-acting insulin. In contrast, insulin glargine provides more predictable 24-hour coverage with lower hypoglycemia risk. Due to its acidic pH, it forms aggregates upon subcutaneous injection, causing prolonged absorption. Insulin detemir, another analog, has a smoother time-action profile and reduced hypoglycemia prevalence compared to NPH insulin. Insulin degludec, a modified insulin, forms multihexamers post-injection, leading to less severe hypoglycemia than glargine.

Insulin is primarily administered subcutaneously, often via popular prefilled pen devices or needle-free jet injectors. Intravenous insulin infusions benefit ketoacidosis patients or during rapidly changing insulin requirements, such as in intensive care or the perioperative period. However, due to its specific absorption and action profile, long-acting insulin should not be given intravenously, intramuscularly, or through an infusion device.

Insulin preparations, based on their duration of action, are categorized as short-acting and long-acting.

Short-acting regular insulin forms hexamers, slowing its absorption, and is given 30-45 minutes before a meal. In contrast, short-acting insulin analogs like lispro, aspart, and glulisine are injected just before meals. They dissociate into monomers, resulting in quicker absorption and rapid action.

An intermediate-acting NPH contains an insulin suspension complexed with zinc and protamine, which, upon administration, dissolves gradually, prolonging its action up to 10-20 hours.

In comparison, long-acting analogs, such as glargine, detemir, and degludec, provide extended insulin coverage and lower hypoglycemia risk.

Typically, pens or needle-free jet injectors subcutaneously inject an insulin preparation.

Also, continuous subcutaneous insulin infusion pumps deliver only short-acting insulins, improving glucose control overnight, between meals, and during exercise.

Additionally, intravenous infusions of regular insulin regulate glucose in diabetic ketoacidosis patients and during perioperative procedures.