Insulin Glargine

Insulin glargine is a long-acting human insulin analogue given subcutaneously once daily as basal insulin. It has a flat, peakless profile that lowers nocturnal hypoglycaemia compared with NPH insulin, and a more concentrated form (300 units/mL) has an even longer, flatter action. It is first-line basal insulin in many settings, with several biosimilars.

Classification. Long-acting insulin analogue; two arginine residues are added at the B chain terminus and glycine replaces asparagine at A21, which shifts the isoelectric point so that the insulin precipitates at body pH. U100 pens and vials; U300 pens; fixed-dose combinations with GLP-1 receptor agonists exist.

Mechanism. Binds the insulin receptor with the same effects as human insulin. Slow dissolution of the subcutaneous precipitate gives a steady release.

Pharmacodynamics. U100: onset 2 to 4 hours, no pronounced peak, duration 20 to 24 hours. U300: onset about 6 hours, duration up to 36 hours, steady state after 3 to 4 days.

Pharmacokinetics. Metabolised in the subcutaneous tissue to active metabolites M1 and M2. Cleared by the liver and kidney.

Type 2 diabetes, adults.

• Start 10 units, or 0.1 to 0.2 unit/kg, subcutaneously once daily at the same time each day (bedtime or morning).
• Titrate by 2 units every 3 days (4 units if fasting glucose is over 10 mmol/L) to a fasting glucose of 4 to 7 mmol/L (about 70 to 130 mg/dL). 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; add prandial insulin or another agent rather than raising basal insulin further.
• U300 titration is no more often than every 3 to 4 days because steady state is slower.

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 glargine once daily, with rapid-acting insulin before meals.
• Titrate by 1 to 2 units, or 10 to 15%, every 3 days.

Switching.

• From once-daily NPH insulin: same unit dose. From twice-daily NPH insulin: start at about 80% of the total NPH dose.
• From U100 to U300: start at the same unit dose and expect to need about 10 to 18% more, titrated over days.

Children and adolescents with type 1 diabetes (licensed from 2 years for U100 and from 6 years for U300).

• 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 glargine 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). Observe for at least 24 hours after large doses because the effect lasts.

Other serious adverse effects.

• Weight gain; lipohypertrophy at repeated injection sites with erratic absorption; rotate sites.
• Rare insulin allergy and injection site reactions; fluid retention with pioglitazone.
• Not for intravenous use or for ketoacidosis.

Common prescribing errors.

• Mixing insulin glargine with any other insulin or diluting it; the acidic solution precipitates.
• Drawing U300 insulin out of a pen with a syringe, which gives the wrong dose.
• Using a syringe that does not match the vial concentration, or confusing units with millilitres.
• Giving the basal insulin dose before meals as a mealtime dose, or confusing the basal pen with the rapid-acting pen.

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: acceptable when better-studied options are not available; NPH insulin and insulin detemir are used more often. Needs rise from the second trimester and fall sharply after delivery.
• Breastfeeding: compatible; needs fall in lactation.
• Children: from 2 years (U100) and 6 years (U300) in many markets.
• Older adults: lowers nocturnal hypoglycaemia compared with NPH insulin; relax targets.
• Kidney impairment: reduce doses; prolonged action.
• Liver impairment: reduce doses.
• East Africa: costlier than NPH insulin but increasingly available as biosimilar products. Unopened pens and vials keep in a fridge (2 to 8 degrees Celsius); an in-use U100 pen or vial keeps at room temperature up to 30 degrees Celsius for 28 days and an in-use U300 pen for 56 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; never draw U300 insulin into a syringe.

Subcutaneous administration. Inject into the abdomen, thigh or upper arm once daily at the same time each day; rotate sites. 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, and when starting a GLP-1 receptor agonist or an SGLT2 inhibitor.

Referral and escalation. Admit severe hypoglycaemia, ketoacidosis or glucose over 25 mmol/L (450 mg/dL) with illness. Refer to a diabetes specialist when a total basal dose over 0.5 unit/kg fails to reach target.