Insulins

Products

Insulins are primarily commercially available in the form of clear injection solutions and turbid injection suspensions (vials, cartridges for pens, ready-to-use pens). In some countries, inhalation preparations are also available. However, these are an exception. Insulins should be stored in a refrigerator at 2 to 8°C (see under Refrigerated Storage). They must not be frozen under any circumstances. Once opened, they may be stored at room temperature for a period of time, usually one month. They should not be exposed to sunlight and should not be stored in a car. Insulins were introduced in the 1920s. They were initially extracted from the pancreas of animals (porcine insulin, bovine insulin). Today, they are mainly produced using biotechnological methods. Recombinant insulin has been available since the 1980s. Biosimilars of some insulins are available today.

Structure and properties

Insulin is a small protein produced by beta cells in the pancreas of humans. The polypeptide is composed of two chains with a total of 51 amino acids. The A chain is composed of 21 amino acids and the B chain is composed of 30 amino acids. Insulin has two disulfide bridges connecting the chains and one disulfide chain within the A chain. In addition to human insulin, there are also so-called insulin analogues on the market, which differ slightly structurally from the natural hormone. For example, individual amino acids are removed or replaced by others. This leads to a change in pharmacokinetic properties.

Effects

Insulins (ATC A10A) have blood glucose-lowering and antidiabetic properties. They promote the uptake of blood glucose into tissues (eg, muscle, adipose tissue). The effects are based on binding to insulin receptors. Insulin analogs differ from human insulin in onset of action (10 to 60 minutes), duration of action (3 to 36 hours), maximum effect (peak), and extent of blood glucose lowering:

• Meal insulins (prandial insulins, bolus insulins) have a rapid onset of action and a short duration of action. They are administered before meals.
• Basal insulins have a long duration of action and are injected once daily.

Mixed insulins contain a fixed combination of short- and long-acting insulins. They are usually injected in the morning and evening. Isophane insulins (= NPH insulins) are complexed with protamine and have a later onset and longer duration of action than ordinary insulin. They belong to the group of delayed-action insulins. They are also included in mixed insulins.

Indications

For the treatment of type 1 diabetes or type 2 diabetes.

Dosage

According to the professional information. The amount to be injected is determined individually. It depends on various factors (e.g., body weight, physical activity, type of meal, diseases, stress). The blood glucose level must be checked daily. Due to insufficient oral bioavailability, insulins are usually administered subcutaneously, e.g. in the area of the abdomen, thigh or buttocks. Patients are not allowed to inject them intravenously. The injection site and needle should be changed with each injection and there should be no massage. The timing of administration depends on the active ingredient and the dosage form. They are administered with insulin pens, insulin pumps, and less commonly, insulin syringes from vials. Insulin can also be inhaled (see Inhalable Insulin).

Active Ingredients

Recombinant human insulin:

• Human insulin (e.g., huminsulin).

Insulin analogues: short-acting and rapid-acting insulin analogues (meal insulins, prandial insulins, bolus insulins):

• Insulin aspart (NovoRapid).
• Insulin lispro (Humalog)
• Insulin glulisine (Apidra)

Long-acting insulin analogues (basal insulins):

• Insulin detemir (Levemir).
• Insulin glargine (Lantus, biosimilars).
• Insulin degludec (Tresiba)

Insulins of animal origin:

• Porcine insulin (Insulin Hypurin Porcine, out of trade).
• Bovine insulin (in many countries out of trade).

Isophane insulin Mixed insulins (eg, Humalog Mix) Inhalable insulin (Afrezza).

Contraindications

Insulins are contraindicated in hypersensitivity, hypoglycemia, and insulinoma.Full details of precautions and interactions can be found in the Drug Information Leaflet. Numerous drugs have an effect on blood glucose.

Adverse effects

The most common potential adverse effects include hypoglycemia and injection site reactions such as redness, pain, itching, swelling, inflammation, and lipodystrophy.