Premixed Insulin Prescribing

Premixed insulin combines a short-acting or rapid-acting component with an intermediate-acting protamine component in one injection. It reduces the number of injections and is common in East Africa, but it fixes the ratio of mealtime to basal insulin and requires regular meals.

Types. Biphasic human insulin 30/70 (30% soluble, 70% isophane). Biphasic analogue mixes 25/75 and 30/70 (aspart or lispro with protamine). Some 50/50 mixes.

Indications. Type 2 diabetes with insufficient control on basal insulin, patients with regular meal patterns, or patients unable to manage basal bolus injections.

Poorly suited. Type 1 diabetes (use basal bolus when possible), irregular meals, shift work, and patients with frequent hypoglycaemia.

Concurrent drugs. Continue metformin. Stop or reduce sulphonylureas to limit hypoglycaemia.

Once daily start. 10 units, or 0.2 units/kg, with the evening meal, or 6 units before the largest meal.

Twice daily start. 0.2 to 0.3 units/kg total daily, split two thirds before breakfast and one third before dinner (or half and half), given before the morning and evening meals.

Timing. Inject human mixes 30 minutes before eating. Inject analogue mixes immediately before or within 15 minutes of starting a meal.

Titration. - Adjust the morning dose by the pre-dinner glucose and the evening dose by the fasting glucose. - Increase by 2 units every 3 days until pre-meal glucose is 4 to 7 mmol/L. - Reduce by 10 to 20% for any glucose under 4 mmol/L. - Cap the total daily dose at about 1 unit/kg and then reassess the regimen.

Mixing before injection. Roll the pen or vial gently 10 times and invert 10 times until the suspension is uniformly cloudy. Do not shake vigorously.

Special groups. - Kidney impairment: reduce dose by 25% at eGFR 10 to 50. - Liver disease: lower doses with cautious titration. - Pregnancy: not usually preferred; use basal bolus. - Breastfeeding: compatible. - Older adults: once daily before the evening meal; relax targets. - Fasting during Ramadan: reduce the morning dose and take the evening dose at the evening meal, with specialist review.

Monitoring. Capillary glucose before breakfast and dinner, plus occasional bedtime and 03:00 checks. HbA1c every 3 months. Watch for weight gain.

Switching. Move to basal bolus if hypoglycaemia is frequent, meals are irregular, or glucose between meals is not controlled. Move to basal insulin with a GLP 1 receptor agonist if weight and hypoglycaemia are concerns.

Stopping. Stop or reduce for recurrent glucose under 4 mmol/L, falling insulin requirements, or intercurrent illness with reduced intake.

Referral and escalation. Refer if dose exceeds 1 unit/kg without control, for recurrent hypoglycaemia, or for ketosis.