Insulin

Key examples

• Insulin aspart
• Insulin glargine
• Biphasic insulin
• Soluble insulin

 

Common indications

1. For insulin replacement in people with type 1 diabetes mellitus and control of blood glucose in people with type 2 diabetes mellitus where oral hypoglycaemic treatment is inadequate or poorly tolerated.
2. Given intravenously, in the treatment of diabetic emergencies such as diabetic ketoacidosis and hyperglycaemic hyperosmolar syndrome, and for perioperative glycaemic control in selected diabetic patients.
3. Alongside glucose to treat hyperkalaemia, while other measures (such as treatment of the underlying cause) are initiated.

 

Mechanisms of action

• In diabetes mellitus, exogenous insulin functions similarly to endogenous insulin. It stimulates glucose uptake from the circulation into tissues, including skeletal muscle and fat, and increases use of glucose as an energy source. Insulin stimulates glycogen, lipid and protein synthesis and inhibits gluconeogenesis and ketogenesis. For the treatment of hyperkalaemia, insulin drives K+ into cells, reducing serum K+ concentrations. However, once insulin treatment is stopped, K+ leaks back out of the cells into the circulation, so this is a short-term measure while other treatment is commenced.
• The wide choice of insulin preparations for treatment of diabetes mellitus can be classified as: rapid acting (immediate onset, short duration): insulin aspart, e.g. Novorapid®; short acting (early onset, short duration): soluble insulin, e.g. Actrapid®; intermediate acting (intermediate onset and duration): isophane (NPH) insulin, e.g. Humulin I®; and long acting (flat profile with regular administration): insulin glargine (Lantus®), insulin detemir (Levemir®). Biphasic insulin preparations contain a mixture of rapid- and intermediate-acting insulins, e.g. Novomix® 30 (insulin aspart/insulin aspart protamine).
• Where IV insulin is required (hyperkalaemia, diabetic emergencies, peri-operative glucose control), soluble insulin (Actrapid®) is usually used.

 

Important adverse effects

• The main adverse effect of insulin is hypoglycaemia, which can be severe enough to lead to coma and death. When administered by repeated subcutaneous (SC) injection at the same site, insulin can cause fat overgrowth (lipohypertrophy), which may be unsightly or uncomfortable.

 

Warnings

• In patients with renal impairment, insulin clearance is reduced, so there is an increased risk of hypoglycaemia.

 

Important interactions

• Although often necessary, combining insulin with other hypoglycaemic agents increases the risk of hypoglycaemia. 
• Concurrent therapy with systemic corticosteroids increases insulin requirements.