Premixed and co-formulated insulin

Alternative to bolus insulin when target HbA1c not reached on basal insulin despite fasting glucose levels < 7 mmol/L and/or doses of 0.5 units/kg/day of basal insulin

Should only be used if the patient is eating regular meals - NB: Important to check kai/food security (can use NZ Health Equity test)

Currently available premixed or co-formulated insulins in New Zealand include:
- NovoMix 30 (30% rapid acting insulin/70% basal insulin)
- Humalog Mix 25 (25% rapid acting insulin/75% basal insulin)
- Humalog Mix 50 (50% rapid acting insulin/50% basal insulin)
- Humulin 30/70 (30% short acting insulin/70% basal insulin)
- Ryzodeg 70/30 (30% rapid acting insulin/70% basal insulin)
  - The basal insulin in Ryzodeg is degludec, which is an ultra-long acting insulin with a half-life of 25 hours. Therefore, Ryzodeg should not be used more than twice daily and caution is recommended in the elderly and those with renal impairment
- NB: NovoMix 30 is planned to be phased out of New Zealand in early 2026
The choice of premixed insulin is dependent on the desired insulin profile for the patient.
- Premixed or co-formulated insulins containing rapid acting insulin are generally preferred due to the reduced risk of delayed hypoglycaemia.
- Humalog Mix 50 may be useful when the premixed insulin is administered with a large carbohydrate based meal, particularly if significant persistent postprandial hyperglycaemia with the 25% or 30% mixes.
- Ryzodeg is likely useful for people who have predominantly one large meal per day and/or where only one injection per day is desirable

Start once daily premixed or co-formulated insulin if predominantly one large meal per day

Convert daily dose of basal insulin to premixed or co-formulated insulin before largest meal
Monitor glucose levels before and 2-3 hours after that meal via capillary blood glucose levels or continuous glucose monitoring
If adherent and correct injection technique, increase dose by 10% if on 3 checks glucose levels rise by > 3 mmol/L with meal AND fasting glucose level is > 10 mmol/L
NB: Dose changes can be made every 3 consecutive checks i.e. every 3 days if needed. Due to the longer half life of degludec insulin, doses of Ryzodeg should be adjusted at whatever interval between 3 - 7 days is practical.

Convert daily dose of basal insulin to premixed or co-formulated insulin with half the dose pre-breakfast and half pre-dinner
Consider alternative ratio if large difference in meal sizes (e.g. 2/3rd of total daily insulin at larger meal and 1/3rd of total daily insulin at smaller meal) and lower evening dose in elderly
Monitor glucose levels before and 2-3 hours after breakfast and dinner via capillary blood glucose levels or continuous glucose monitoring
If adherent + correct injection technique then:
- Increase breakfast dose by 10% if on 3 checks glucose levels rise with breakfast by > 3 mmol/L AND pre-dinner glucose is > 10 mmol/L
- Increase dinner dose by 10% if on 3 checks glucose levels rise with dinner by > 3 mmol/L AND pre-breakfast glucose level is > 10 mmol/L
- NB: Dose changes can be made every 3 consecutive checks i.e. every 3 days if needed. Due to the longer half life of degludec insulin, doses of Ryzodeg should be adjusted at whatever interval between 3 - 7 days is practical.

NB: Premixed insulin needs to be mixed by gently inverting before each use
- Ryzodeg does not need to be mixed as it is a co-formulation rather than a premixed suspension

Stop sulfonylureas once established on premixed insulin, but continue lifestyle management and other glucose lowering therapies

Provide clear instructions for patients on how to self-titrate and administer premixed insulin

Clear instructions for patients on how to administer and self-titrate bolus insulin

Essential particularly if concerns over cognitive impairment (medication oversight may be required)
Administer before meals
Patients should be advised that they will likely need to reduce the dose of premixed insulin if they are having significantly less than normal intake at that meal
Patients should have different coloured pens for their different types of insulin
Use BD fine 4 or 5 mm needles as associated with better absorption and less pain/trauma
Encourage rotation of injection sites
Explain that doses of premixed insulin may need to be reduced for meals immediately before and after strenuous exercise
Memory adjuncts (e.g. NovoPen Echo; InsulCheck etc.) may be useful

Consider referral to dietitian for ‘carbohydrate awareness’ and matching of insulin to carbohydrate intake

Consider switching one or both injections to Humalog Mix 50 if significant postprandial hyperglycaemia and titrate as above
Consider adding in bolus insulin at other meals if glucose levels rise by > 3 mmol/L at these times (e.g. lunch, large snacks)

Ensure adherence to all therapy
Review lifestyle management and provide ongoing support to improve this
Check injection technique and injection sites
Re-refer to dietitian
Optimise non-insulin glucose lowering therapies
Strongly consider converting to basal bolus regimen particularly if problems with hypoglycaemia and/or irregularity in diet
Screen for depression and diabetes distress

Convert daily dose of premixed insulin to 50% as once daily basal insulin and 50% as bolus insulin split between meals

E.g. Premixed insulin 25 units mane 35 units nocte → 30 units basal insulin nocte + 10 units of bolus insulin with meals

May need to alter starting doses of bolus insulin based on different meal sizes across the day
Titrate doses of basal and bolus insulin as required
The doses of premixed insulin will likely need to be reduced if major changes in diet (e.g. Ramadan) or if new glucose lowering therapies are added to the regimen

Type 2 Diabetes Management Guidelines