Insulin Detemir

Insulin detemir is a long-acting human insulin analogue given subcutaneously once or twice daily as basal insulin. It binds albumin, which gives a smoother profile than NPH insulin with less nocturnal hypoglycaemia and less weight gain than other basal insulins. It is licensed in pregnancy in many markets. The product has been withdrawn in several markets, so availability is falling.

Classification. Long-acting insulin analogue; threonine at B30 is removed and a 14-carbon fatty acid (myristic acid) is attached at B29, allowing albumin binding. U100 pens and vials.

Mechanism. Binds the insulin receptor with the same effects as human insulin. Reversible binding to albumin in the subcutaneous tissue and the circulation delays and smooths action.

Pharmacodynamics. Onset 1 to 2 hours; duration dose dependent, about 12 hours at 0.2 unit/kg and up to 20 to 24 hours at 0.4 unit/kg. Less peaked than NPH insulin; within-patient variability is lower.

Pharmacokinetics. Peak 6 to 8 hours; over 98% albumin bound; half-life 5 to 7 hours. Cleared by the liver and kidney.

Type 2 diabetes, adults.

• Start 10 units, or 0.1 to 0.2 unit/kg, subcutaneously once daily in the evening (with the evening meal or at bedtime), or in the morning.
• Titrate by 2 to 4 units every 3 days to a fasting glucose of 4 to 7 mmol/L (about 70 to 130 mg/dL). Move to twice daily (morning and evening, 12 hours apart) when daily doses exceed about 0.4 unit/kg or control is poor late in the day.
• Reduce the dose by 10 to 20% after any hypoglycaemia. No fixed maximum; a total basal dose over 0.5 unit/kg suggests over-basalisation.

Type 1 diabetes, adults.

• Total daily insulin about 0.4 to 1 unit/kg, commonly 0.5 unit/kg; about 40 to 50% as insulin detemir given twice daily, with rapid-acting insulin before meals.
• Titrate by 1 to 2 units, or 10 to 15%, every 3 days.

Switching. From NPH insulin or insulin glargine: unit for unit, with the same schedule (twice daily if on twice-daily NPH insulin); adjust over the next week.

Pregnancy. Used in type 1 and type 2 diabetes, with outcomes comparable to NPH insulin and less hypoglycaemia. Continue at the pre-pregnancy dose; needs rise from the second trimester.

Children and adolescents with type 1 diabetes (licensed from 1 to 2 years depending on the market).

• Basal dose about 30 to 50% of the total daily insulin of 0.7 to 1 unit/kg before puberty and up to 1.2 unit/kg in puberty; directed by a paediatric diabetes team.

Adjustments.

• Kidney: reduce dose by about 25% when eGFR is 10 to 50 and about 50% when under 10, adjusted to glucose.
• Liver: reduce dose in cirrhosis and acute liver failure.
• Older adults: start 10 units or less; use less strict targets.
• Weight: dose by weight in children.

Contraindications. Hypoglycaemia; hypersensitivity to insulin detemir or an excipient (rare).

Hypoglycaemia. The main risk. Treat glucose under 4 mmol/L (70 mg/dL) with 15 to 20 g fast oral glucose and recheck at 15 minutes. For severe hypoglycaemia give intravenous glucose 10% 150 to 200 mL over 15 minutes, or glucagon 1 mg intramuscularly or subcutaneously (0.5 mg for children under 25 kg).

Other serious adverse effects.

• Injection site reactions, which are more frequent than with other basal insulins; lipohypertrophy at repeated injection sites; rotate sites.
• Weight gain (less than with NPH insulin or insulin glargine); rare insulin allergy; fluid retention with pioglitazone.
• Not for intravenous use or for ketoacidosis.

Common prescribing errors.

• Mixing insulin detemir with other insulins.
• Using a syringe that does not match the vial concentration, or confusing units with millilitres.
• Confusing the basal pen with the rapid-acting pen.
• Assuming a once-daily dose will last 24 hours at low doses; many patients need twice-daily dosing.

Major interactions.

• Increased hypoglycaemia: sulphonylureas, ACE inhibitors, fibrates, fluoxetine, monoamine oxidase inhibitors, salicylates, alcohol.
• Reduced effect: corticosteroids, thiazides, atypical antipsychotics, oestrogen-containing contraceptives, protease inhibitors, thyroid hormones.
• Beta-blockers mask hypoglycaemia symptoms.
• Pioglitazone and insulin together: fluid retention and heart failure.
• GLP-1 receptor agonists and SGLT2 inhibitors: lower the insulin dose when starting.

Special groups.

• Pregnancy: licensed in many markets; effective and safe; needs rise from the second trimester and fall sharply after delivery.
• Breastfeeding: compatible; needs fall in lactation.
• Children: from 1 to 2 years in many markets.
• Older adults: low nocturnal hypoglycaemia risk; relax targets.
• Kidney impairment: reduce doses; prolonged action.
• Liver impairment: reduce doses.
• East Africa: supply is limited and shrinking; insulin glargine or NPH insulin are usual alternatives, and a patient found on insulin detemir needs a transfer plan when stock runs out. Unopened pens and vials keep in a fridge (2 to 8 degrees Celsius); an in-use pen keeps at room temperature up to 30 degrees Celsius for 42 days; protect from direct sunlight and never freeze.

Formulation and preparation. Clear, colourless solution; do not use if cloudy or discoloured. Do not mix with other insulins. Use pens or U100 syringes with U100 vials.

Subcutaneous administration. Inject into the abdomen, thigh or upper arm once or twice daily; rotate sites. Give twice-daily doses about 12 hours apart. Never give intravenously.

Baseline. Capillary glucose, HbA1c, eGFR, hypoglycaemia history.

Monitoring.

• Fasting capillary glucose daily during titration; bedtime and pre-meal glucose when combined with prandial insulin.
• HbA1c every 3 months.
• eGFR at least annually.

Dose reduction and stopping. Reduce the dose by 10 to 20% after any hypoglycaemia without a clear cause. When stock ends, change to another basal insulin at the same unit dose and adjust over the next week.

Referral and escalation. Admit severe hypoglycaemia, ketoacidosis or glucose over 25 mmol/L (450 mg/dL) with illness.