Key points from the evidence

The content of this evidence summary was up-to-date in September 2013. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Summary

The long-acting insulin analogue, insulin degludec, is available in 2 strengths: 100 units/ml and 200 units/ml. It is non-inferior to insulin glargine in terms of glycaemic control in type 1 diabetes, with statistically significantly lower rates of nocturnal hypoglycaemia. Although there is one published 104 week study reporting some safety data, there are no published studies comparing insulin degludec with NPH (isophane) insulin and none that measure patient-oriented efficacy outcomes.

Effectiveness

  • Insulin degludec is non-inferior to insulin glargine for glycaemic control.

  • Insulin degludec reduced HbA1c by between 0.1% points [1 mmol/mol] and 0.4% points [4 mmol/mol] from baseline (2 RCTs, up to 104 weeks).

  • These reductions in HbA1c were non-inferior to insulin glargine.

Safety

  • The MHRA has issued advice to minimise the risk of medication errors associated with the higher strength 200 units/ml formulation.

  • The dose-counter window of the pen device shows the number of units, irrespective of strength. Therefore, no dose conversion is needed.

Patient factors

  • Once daily, with flexibility in timing of administration. SmPC states that a minimum of 8 hours between injections should always be ensured.

  • Similar tolerability to insulin glargine.

  • Statistically significant reductions in nocturnal hypoglycaemia of between 1.4 and 4 episodes per patient per year with insulin degludec compared with insulin glargine (2 RCTs up to 104 weeks).

Resource implications

  • 5×3 ml cartridges (100 units/ml) and 5×3 ml pre-filled pen (100 units/ml), £72.00.

  • 3×3 ml pre-filled pen (200 units/ml), £86.40.

  • More expensive than NPH (isophane) insulin, insulin glargine and insulin detemir.

Key points

Insulin degludec (Tresiba) is a long-acting insulin analogue that has been marketed in the UK for basal insulin therapy in adults (18 years or over) with type 1 or type 2 diabetes. It is available in 2 strengths: 100 units/ml and 200 units/ml. This evidence summary considers the use of insulin degludec in adults with type 1 diabetes. It supersedes an earlier evidence summary (ESNM5), published in November 2012. Another evidence summary considers its use in adults with type 2 diabetes.

This evidence summary is based on 2 randomised controlled trials (RCTs) in which insulin degludec was compared with insulin glargine (Heller et al. 2012 and Bode et al. 2013; and Mathieu et al. 2013).

Evidence from the 2 open-label RCTs indicates that insulin degludec is non-inferior to insulin glargine in terms of glycaemic control: both basal insulins reduced glycated haemoglobin (HbA1c) levels to a similar degree (as would be expected with a treat-to-target trial design). With regard to hypoglycaemia, insulin degludec statistically significantly reduced the rate of nocturnal hypoglycaemia compared with insulin glargine. However, the absolute difference in this rate was small (between 1.4 and 4 episodes per patient per year at up to 104 weeks) and the trials failed to find a difference in the rates of overall, daytime or severe hypoglycaemia. There are no published studies comparing insulin degludec with NPH (isophane) insulin and none that measure patient-oriented efficacy outcomes.

Insulin degludec is given once daily at any time of the day, preferably at the same time every day. On occasions when this is not possible, there can be some flexibility in the timing of insulin administration. The Summary of product Characteristics states that a minimum of 8 hours between injections should always be ensured.

Insulin degludec is the first insulin approved in Europe at a higher strength than the European Union-wide standard of 100 units/ml. The Medicines and Healthcare Products Regulatory Agency (MHRA) has issued advice to minimise the risk of medication errors associated with the 200 units/ml formulation. The dose-counter window of the pen device shows the number of units that will be injected, irrespective of strength. Therefore, no dose conversion is needed when transferring a person from one strength of insulin degludec to another.

Type 1 diabetes: diagnosis and management of type 1 diabetes in children, young people and adults (NICE clinical guideline 15; which is currently being updated) recommends that basal insulin supply for adults should be provided by using NPH (isophane) insulin or a long-acting insulin analogue. Examples of NPH (isophane) insulin include Insulatard, Humulin I or Insuman Basal. NICE recommends that a long-acting insulin analogue should be used when:

  • nocturnal hypoglycaemia is a problem on NPH (isophane) insulin

  • morning hyperglycaemia on NPH (isophane) insulin results in difficult daytime blood glucose control

  • rapid-acting insulin analogues are used for mealtime blood glucose control.

Insulin degludec will be included in the update of this guideline, the publication date of which is still to be confirmed.

Local decision makers will need to consider the evidence for insulin degludec in type 1 diabetes alongside that for other basal insulins. Individual patient factors and their experience of hypoglycaemia together with the higher cost of insulin degludec will need to be taken into account.

Update

The following information has become available since this ESNM was produced.

April 2015: High strength, fixed combination and biosimilar insulin products minimising the risk of medication error

The MHRA has issued advice on how to minimise the risk of medication errors with high strength, fixed combination or biosimilar insulin products. Insulin degludec is available in 2 strengths and as a fixed combination product with liraglutide. See the Drug Safety Update April 2015 for more information.

August 2015: Updated NICE guideline on type 1 diabetes published

The updated NICE guideline on type 1 diabetes in adults: diagnosis and management has now been published. The guideline does not give any specific recommendations on the use of insulin degludec in type 1 diabetes. See the NICE guideline for more information.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.