Long Acting Insulin Analogues

Long acting insulin analogues (insulin glargine U100 and insulin detemir) give a flatter basal profile than isophane insulin, covering baseline requirements with once or twice daily injection.

Mechanism. Receptor activity matches human insulin. Glargine is soluble at acidic pH and precipitates at the neutral pH of subcutaneous tissue, forming a slow-release depot. Detemir carries a fatty acid chain that binds albumin, delaying distribution.

Pharmacokinetics. Glargine U100: onset 1 to 2 hours, no marked peak, duration about 20 to 24 hours. Detemir: duration 12 to 24 hours, dose-dependent, with small doses often needing twice daily administration. Glargine must not be mixed with other insulins or diluted.

Glargine U100. Once daily at a consistent time. Biosimilar forms are available.

Detemir. Shorter duration, so twice daily in many patients with type 1 diabetes. Weight gain is lower than with glargine and the day to day variability is smaller. Availability has contracted in some markets, so confirm local supply.

Versus isophane. Lower nocturnal hypoglycaemia, no resuspension and once daily dosing.

Versus ultra long analogues. Shorter duration, so the dose should be given at a consistent time each day. Steady state is reached in 2 to 4 days.

• Type 2 diabetes: start 10 units daily or 0.2 units/kg, increase by 2 units every 3 days to a fasting glucose of 4.4 to 7.2 mmol/L (80 to 130 mg/dL), or by 4 units if fasting glucose is over 10 mmol/L (180 mg/dL). Reduce by 10 to 20% after any hypoglycaemia.
• Type 1 diabetes: about 40 to 50% of the total daily dose, with mealtime rapid insulin.
• Switching from twice daily isophane to once daily glargine: reduce the total dose by about 20%. Once daily isophane to glargine is unit for unit.
• Overbasalisation: a basal dose over 0.5 units/kg, a bedtime to morning glucose fall of 3.3 mmol/L (50 mg/dL) or more, or recurrent hypoglycaemia indicates the need for mealtime insulin or another agent, rather than basal increase.
• Hospital: the basal dose is continued, and at about 80% of the usual dose when oral intake is reduced; omission in type 1 diabetes risks ketoacidosis.

Special groups. Pregnancy: detemir is licensed, and glargine is widely used without harm signals. Breastfeeding: compatible. Children: used from early childhood. Older adults: preferred basal choice because of lower nocturnal hypoglycaemia. Kidney impairment: reduce dose by 25 to 50%. Liver impairment: reduce dose.

Adverse effects. Hypoglycaemia, weight gain, lipohypertrophy and injection site pain, which is more frequent with glargine because of the acidic solution. No cancer signal has been shown in the large studies of glargine despite higher IGF-1 receptor binding in vitro.

Key errors. Mixing glargine with other insulins in one syringe, switching products without checking doses, and giving detemir once daily at doses that do not last 24 hours.

Monitoring. Fasting glucose daily during titration, bedtime and 3 a.m. glucose where nocturnal hypoglycaemia is suspected, HbA1c every 3 months.

Referral and escalation. Total daily insulin over 1 unit/kg without control, recurrent hypoglycaemia, or unexplained variability.