Abstract

Insulin is an anabolic peptide hormone that is produced and secreted from beta cells located in the islets of Langerhans of the pancreas. It has important metabolic functions, which include promoting the storage of carbohydrates, amino acids, and fat in the liver, skeletal muscle, and adipose tissues. By modulating glucose absorption from the blood, insulin lowers blood glucose levels. Insulin therapy is an important part of treatment for individuals with insufficient or absent insulin production (e.g., diabetes mellitus, gestational diabetes). Several insulin analogs (e.g., insulin glargine) are available that are related to human insulin but have a different molecular structure and differ in onset, peak, and duration compared to human insulin. It is crucial that patients receiving insulin therapy undergo in-depth training to prevent potentially life-threatening conditions such as hypoglycemia as a result of an insulin overdose or drug interactions.

For further information on insulin therapy and regimens, see insulin therapy.

Overview

Types of insulinand trade names	Effect	Application	Special features
Rapid-acting insulin
Insulin lispro	Onset: 5–30 min Peak: 30 min–3 h Duration: 3–5 h	Intensified conventional insulin therapy	Injected before a meal time Used in combination with longer-acting insulin
Insulin aspart
Insulin glulisine
Short-acting insulin
Regular insulin	Onset: ∼30 min Peak: 2.5–5 h Duration: 4–24 h	“Standard insulin” for lowering blood glucose levels in an acute setting Conventional insulin therapy Intensified conventional insulin therapy	Mandatory interval between injections and meal times: ∼30 min Used in combination with longer-acting insulin Intravenous therapy available (only for this type of insulin)
Intermediate-acting insulin
NPH insulin	Onset: 1–2 h Peak: 4–12 h Duration: 14–24 h	Conventional insulin therapy Component of basal supported oral therapy (BOT) for treatment-resistant type 2 diabetes mellitus	Crystalline suspension consisting of regular insulin (with a high level of solubility) and protamine (with a low level of solubility) Mandatory interval between injections and meal times: 30–60 min Used in combination with rapid or short-acting insulin Usually administered twice daily
Long-acting insulin
Insulin glargine	Onset: 1.5–4 h Peak: flat; not defined Duration: ∼ 24 h	Intensified conventional insulin therapy Component of basal supported oral therapy (BOT) for treatment-resistant type 2 diabetes mellitus	Insulin analogs More consistent efficacy profile and longer duration of effect compared to NPH insulin due to different modes of action Glargine: formation of precipitates that slowly dissolve at the injection site Detemir: interaction with serum albumin Degludec: formation of slowly dissolving multi-hexamers Used in combination with rapid or short-acting insulin Administered once or twice daily
Insulin detemir
Insulin degludec
Ultralente insulin
Mixed insulin
Mixed insulin	Biphasic effect Short-term effect like that of regular insulin/lispro/aspart Long-term effect like that of NPH insulin	Conventional insulin therapy	Contains regular insulin and NPH insulin mixed according to a defined ratio Example: Actraphane^® 30/70, contains 30% regular insulin and 70% NPH insulin Some manufacturers only add one number to the trade name, e.g., Insuman^® Comb 25 Administered two or three times a day

Some manufacturers use the same trade name for both regular insulin and mixed insulin (with a varying amount of NPH insulin). The package insert should be read carefully!

Effects

Insulin is an anabolic peptide hormone; that is produced and secreted from beta cells in the islets of Langerhans of the pancreas in response to a rise in blood glucose
Several insulin analogs (e.g., insulin glargine) are available that are related to human insulin but have a different molecular structure; after injection they exert the same actions but differ in onset, peak and duration compared to human insulin
Insulin binds to insulin receptors (a type of tyrosine kinase receptor) located in various tissues in the body (e.g., liver, skeletal muscle, adipose tissue) and has the following actions:

	Increases	Decreases
Carbohydrate metabolism	Uptake of glucose into cell Glycogenesis Glycolysis	Glycogenolysis Gluconeogenesis: via dephosphorylation of fructose-1,6-bisphosphatase
Lipid metabolism	Lipid synthesis	Lipolysis Ketogenesis
Protein metabolism	Protein synthesis Uptake of amino acids	Proteolysis
Other effects	Secretion of gastric acid Cell growth and differentiation Uptake of potassium

References:^[1]^[2]

Side effects

Hypoglycemia
Weight gain
Lipodystrophy at the injection site
Pain and erythema at injection site
Hypokalemia
Allergic reactions (rare)
Edema (rare)

We list the most important adverse effects. The selection is not exhaustive.

Indications

Type 1 diabetes mellitus
Type 2 diabetes mellitus, if weight normalization, physical activity, and oral antidiabetic drugs do not keep blood glucose levels in the target range
- All type 2 diabetic patients with end stage renal failure (oral antidiabetic drugs are contraindicated in this case)
Pancreatic insufficiency with secondary diabetes
Gestational diabetes, if change of diet is not sufficient
Acute hyperkalemia: A drip containing regular insulin and a solution of glucose reduces blood potassium levels.
See also “insulin therapy” in diabetes mellitus.

Interactions

Insulin demand	Drug
Increased	Thiazide diuretics and loop diuretics Heparin Glucocorticoids Immunosuppressive drugs (calcineurin inhibitors) Tricyclic antidepressants Antipsychotic drugs Lithium HIV-protease inhibitors Thyroid hormones Estrogen (contraceptives) Sympathomimetic drugs that interact with the beta-1 adrenergic receptor (e.g., dobutamine) Derivatives of nicotinic acid
Decreased	Analgesics NSAIDs Tramadol Antibiotics Cotrimoxazole and other sulfonamides (especially in high doses or in cases of renal failure) Fluoroquinolones Antimalarial drugs (e.g., mefloquine, quinine) MAO inhibitors Fibrates Haloperidol
Either increased or decreased	Ethanol Beta blockers

Pharmacokinetics

Absorption: The absorption time determines the onset, peak, and duration of effect.
Prolonged absorption time
- Low temperature
- Obesity
- Peripheral injection site
- Superficial subcutaneous injection
Shorter absorption time
- Manipulative therapy (e.g., massages)
- Deep subcutaneous injection
- Injection into the abdominal skin around the navel