From the 1st August 2018, a new insulin preparation is available on the Pharmaceutical Benefits Scheme (PBS). Ryzodeg® 70/30 is a soluble insulin analogue containing 70% ultra-long-acting basal insulin and 30% rapid-acting prandial insulin.

The rapid-acting component is insulin aspart, which is widely used in Australia in the form of NovoRapid® and the biphasic NovoMix®. The ultra-long-acting component is a new generation insulin called insulin degludec. Upon subcutaneous injection, insulin degludec self-associates into soluble multi-hexamers that function as a depot. Insulin degludec is then slowly and continuously absorbed into the circulation to provide a flat and stable glucose-lowering effect. In comparison, insulin glargine forms micro-precipitates upon subcutaneous injection. Re-dissolution must then occur before it can be absorbed, leading to some inherent variability.

Five pivotal clinical trials evaluated the safety and efficacy of Ryzodeg® in patients with Type 1 and Type 2 diabetes. Non-inferiority for HbA1c change from baseline was confirmed compared to insulin glargine, biphasic insulin aspart, and insulin detemir. Prandial glucose control at the dosing meal was superior for Ryzodeg® compared to insulin glargine owing to the insulin aspart component. Rates of nocturnal hypoglycaemia were lower compared to all comparators. However, the overall rate of confirmed hypoglycaemic events was significantly higher compared to insulin glargine when Ryzodeg® was administered with breakfast. This highlights the importance of tailoring therapy to the individual and administering with main meals.

Ryzodeg® can be given once or twice daily with meals. When given once daily, it should be administered with the largest meal of the day. Close glucose monitoring is recommended upon initiation of Ryzodeg® and adjustments to concomitant anti-diabetic therapy may be required.

A summary of key pharmacokinetic data for long-acting insulins and Ryzodeg® can be found in Table 1.

Table 1. A comparison of longer-acting insulins.

Insulin Detemir Insulin Glargine Insulin Degludec Insulin degludec/insulin aspart
100 IU/mL 300 IU/mL
Onset (hours) 1-2 1-2 1-6 0.5-1.5 0.25**
Time to peak (hours) 6-8 No peak No peak 2.3
Duration (hours) 12-24 24 24-36 >24 >24
Terminal half-life (hours) 5-7 13.5* 19 25.4 25.4***

*Dose-dependent
**Onset of action of the rapid-acting component
***Half-life of the basal component

References:

  1. Haahr H, Heise T. A review of the Pharmacological Properties of insulin degludec and their clinical relevance. Clin Pharmacokint. 2014; 53(9): 787-800.
  2. Kumar A, Franek E, Wise J, Niemeyer M, Mersebach H, Simó R. Efficacy and safety of once-daily insulin degludec/insulin aspart versus insulin glargine (U100) for 52 weeks in insulin-naïve patients with type 2 diabetes: a randomized controlled trial. PLoS One. 2016; 11(10): 0163350.
  3. Rossi S. (Editor). Australian Medicines Handbook. Adelaide: AMH; 2018.
  4. Ryzodeg® (insulin degludec/insulin aspart) Australian approved product information. Baulkham Hills: Novo Nordisk Pharmaceuticals. Approved November 2017.

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