New High Strength Insulins

Several new insulins have come to the market recently; three high strength insulins which have concentrations greater than the previously standard strength of U100 and biosimilar insulin.

The Trustees of IDDT have discussed the introduction of different strengths of insulin in depth and strongly expressed their concerns about the risks of errors by people with diabetes, health professionals and hospitals. These concerns come from their experiences of the introduction of the first genetically modified human insulin in the 1980s when there was a dearth of evidence of benefit and many people with diabetes were not informed of the differences from their previous natural animal insulin.

These new stronger insulins have been largely developed for people who require large doses of insulin to reduce the volume injected and the number of injections.
Here are the details of the new insulins:

Key feature

Active substance

Brand name


Injection device

High strength

Insulin degludec


U100: U200

FlexTouch prefilled pen


Insulin lispro


U100: U200

KwikPen prefilled pen





prefilled pen

Fixed combination

Insulin degludec and liraglutide


Degludec and 3.6mg/mL of liraglutide (Victoza)
U100 cartridge


Prefilled pen


Insulin glargine



Lilly reusable pen
KwikPen prefilled pen

The European Medicines Agency is consulting on safety advice and the MHRA in the UK has stated that it is important that patients and health professionals are aware of the different strengths and how to use them to minimise the risk of medication errors, such as the wrong dose of insulin being injected.

New term – the ‘dose step’
The ‘dose step’ is a new term to define how to dial up the required dose on the prefilled pen.
For Lantus, Toujeo and both strengths of Humalog:

  • one dose step on the prefilled pen is equivalent to one unit of insulin.

In contrast, for Tresiba:

  • one dose step on the U100 pen is equivalent to one unit of Tresiba
  • one dose step on the U 200 pen is equivalent to 2 units of Tresiba.

Dose conversion when switching between standard and high strength insulin products

For all the insulin products in the table above, the required dose is displayed in the dose counter window of the prefilled pen.

  • For Humalog 100 and 200 units/mL KwikPens, and for Tresiba 100 and 200 units/mL FlexTouch pens so there is no need for dose conversion when transferring patients from the standard to high strength version or vice versa.
  • However, Toujeo is not bioequivalent to Lantus so dose adjustment is needed when patients are switched from Lantus or other basal insulins to Toujeo or vice versa.

If you are being changed to a different strength insulin, the MHRA advice to health professionals is worth noting.
Before starting treatment with a high strength, fixed combination or biosimilar insulin::

  • consult the summary of product characteristics and any educational material,
  • ensure that patients read and understand the patient leaflet and any patient education material,
  • ensure that patients receive appropriate training on the correct use of the product,
  • give patients a patient booklet and Insulin Passport (or safety card),
  • warn patients only to use insulin as they have been trained because using it any other way may result in a dangerous overdose or underdose.

Their advice to people with diabetes is obvious – monitor glucose levels closely after starting a new treatment and in the following weeks. You may need to adjust doses and timing of concurrent rapid acting or short acting insulin products and other antidiabetic treatments.

Information on another new insulin – Tresiba

Tresiba (insulin degludec) – no hint of added benefit in children and adolescents
Severe side effects more frequent in girls with Type 1 diabetes and no data for Type 2 diabetes

Tresiba (insulin degludec) has been approved since January 2015 for adolescents and children from the age of one year with Type 1 or Type 2 diabetes. In an early benefit assessment, the German Institute for Quality and Efficiency in Health Care (IQWiG) has now examined whether this new insulin, alone or in combination with other blood-glucose lowering drugs, offers an added benefit over the appropriate comparator treatments.
The findings show:

  • There was no added benefit of Tresiba for adolescents and children with Type 1 diabetes. The manufacturer (NovoNordisk) only presented one study investigating children and adolescents with Type 1 diabetes. The results showed no differences between the treatment groups regarding mortality, symptoms and complaints, as well as most side effects (discontinuation due to side effects, severe and symptomatic hypoglycaemia, ketoacidosis). Health-related quality of life was not investigated. Hence, no suggestion of an added benefit of Tresiba could be derived for these outcomes.
  • In girls there is a suggestion of greater harm regarding serious adverse events. Neither positive nor negative effects were determined for boys. However, in girls with Type 1 diabetes treated with Tresiba serious adverse events occurred more frequently than in the comparator group. Within 52 weeks, severe side effects occurred in approximately 15 of 100 girls who received Tresiba compared with girls who received standard treatment where they occurred in approximately 3 of 100 girls. Hence there is a suggestion of lesser benefit of insulin degludec in girls compared to the appropriate comparator therapy.
  • Novo Nordisk presented no data for adolescents and children with Type 2 diabetes. Therefore there is no suggestion of an added benefit of Tresiba with the appropriate comparator therapy.

Why did IQWiG come to these conclusions?
In this latest dossier for the use of Tresiba in children and adolescents the manufacturer, Novo Nordisk did not differentiate between Type 1 and Type 2 diabetes in the analysis of the study data. This is in contrast to its dossier for the benefit assessment of Tresiba in adults in summer 2014, which did differentiate between Type 1 and Type 2 diabetes in the analysis of study data. Novo Nordisk justified this by claiming that the therapeutic indication was not differentiated in the Summary of Product Characteristics, which generally recommended intensive insulin therapy for adolescents and children.
However, IQWiG did differentiate between Type 1 and Type 2 diabetes in its assessment because these are two different diseases. In Type 1 diabetes, there is an absolute insulin deficiency so that substitution of insulin is vital but in Type 2 diabetes, there is a relative insulin deficiency, which can also be (partly) compensated by other interventions or drugs. This results in different treatment recommendations for the two diseases in the Summary of Product Characteristics, from which children and adolescents are not exempt.

What happens now in Germany?

IQWiG’s dossier assessment is part of the early benefit assessment according to the German Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the Federal Joint Committee (G-BA). After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.

We hope that the MHRA in the UK will be equally diligent in its assessment of Tresiba in children and adolescents.