Key points from the evidence

The content of this evidence summary was up-to-date in October 2015. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Summary

High‑strength insulin products such as insulin glargine 300 units/ml (Toujeo) have been developed for people with large daily insulin requirements to reduce the number and volume of injections. In 1 randomised controlled trial (RCT) in 549 people with type 1 diabetes, Toujeo had similar efficacy to insulin glargine 100 units/ml (Lantus) in terms of HbA1c reduction, but the basal insulin dose used was higher with Toujeo than with Lantus. There was no benefit of Toujeo over Lantus in terms of reduced hypoglycaemic events. The safety profile of Toujeo is largely similar to that of Lantus. Toujeo is not bioequivalent to Lantus and they are not interchangeable without dose adjustment.

Regulatory status: insulin glargine 300 units/ml (Toujeo) received a European marketing authorisation in April 2015. It was launched in the UK in August 2015.

Effectiveness

  • Once‑daily Toujeo was non‑inferior to once‑daily Lantus in HbA1c reduction from baseline to month 6 (difference between groups 0.04% [0.4 mmol/mol], 95% confidence interval [CI] −0.10 to 0.19% [−1.1 to 2.1 mmol/mol]) in people with type 1 diabetes (1 RCT, n=549).

  • Hypoglycaemia (confirmed or severe, nocturnal, or severe) did not differ between Toujeo and Lantus at 6 months in people with type 1 diabetes (1 RCT, n=549).

  • At 6 months the basal insulin dose was approximately 18% higher with Toujeo than with Lantus (1 RCT, n=549).

Safety

  • The safety profile of Toujeo is largely similar to that of Lantus. The most frequent adverse events are nasopharyngitis and upper respiratory tract infection. The most common serious adverse event in people with type 1 diabetes is hypoglycaemia (European public assessment report [EPAR] for Toujeo).

  • In 1 RCT (n=549), similar numbers of participants reported injection site reactions with Toujeo (2.2%) and Lantus (1.5%), and similar numbers withdrew because of adverse events (1.1% in both groups).

Patient factors

  • Toujeo is a high‑strength insulin. It is not simply interchangeable with other long‑acting insulins and there is a potential risk of medication error. However, the dose window of the Toujeo pen shows the number of Toujeo units to be injected. Patients should read and understand the patient leaflet and education material and should have training on the correct use of Toujeo.

  • Toujeo is given once daily, preferably at the same time but can be up to 3 hours before or after usual time.

  • Body weight increased less with Toujeo than with Lantus (mean increase at 6 months 0.5 kg compared with 1.0 kg; p=0.037; 1 RCT, n=549).

  • The higher concentration of insulin in Toujeo means the volume to be injected is smaller, which may be less painful for people injecting large volumes.

Resource implications

  • The cost of Toujeo and other basal insulins will depend on the preparation chosen and the insulin dosage used.

  • The manufacturer has stated that Toujeo has been priced at a level to match the daily cost of Lantus on the basis of average insulin glargine usage in the EDITION trials. The cost of Toujeo is £33.13 for 3×1.5 ml pre‑filled pens (excluding VAT; MIMS, September 2015).

Introduction and current guidance

Type 1 diabetes is a long‑term hormonal deficiency disorder treated with insulin replacement therapy. This is supported by active management of other cardiovascular risk factors, such as hypertension and high circulating lipids.

The updated NICE guideline on type 1 diabetes in adults: diagnosis and management recommends multiple daily injection basal–bolus insulin regimens as the insulin injection regimen of choice for all adults with type 1 diabetes. Twice‑daily insulin detemir is recommended as the preferred basal insulin therapy; with other basal insulin regimens options in certain circumstances (see the guideline for more details).

Full text of Introduction and current guidance.

Product overview

Toujeo is a high‑strength insulin glargine product containing 300 units/ml solution for injection in a pre‑filled pen (Toujeo summary of product characteristics). It is a basal insulin for once‑daily use for the treatment of diabetes mellitus (type 1 and type 2) in adults.

In type 1 diabetes mellitus, it must be combined with short or rapid‑acting insulin to cover mealtime insulin requirements and requires individual dose adjustments.

Toujeo is not bioequivalent to insulin glargine 100 units/ml (Lantus) and dose adjustment is needed when patients are switched from Lantus or other basal insulins to Toujeo or vice versa (MHRA Drug Safety Update April 2015). Toujeo has a flatter and more prolonged (up to 36 hours) profile of insulin concentration and glucose lowering activity compared with Lantus at the same doses (European public assessment report [EPAR] for Toujeo).

Toujeo is available in a pack containing 3 pens. Each pen contains 1.5 ml of insulin glargine 300 units/ml solution for injection, equivalent to 450 units. The cost of a pack of 3 pens is £33.13 (excluding VAT; MIMS, September 2015).

Full text of Product overview.

Evidence review

This evidence summary is based on the main phase 3 study of Toujeo in people with type 1 diabetes (EDITION 4). This RCT was designed to demonstrate non‑inferiority of insulin glargine 300 units/ml (Toujeo) with insulin glargine 100 units/ml (Lantus) in terms of HbA1c reduction in people with type 1 diabetes. The main phase 3 studies of Toujeo in people with type 2 diabetes will be reviewed in the evidence summary on Toujeo for type 2 diabetes (which will be published after the NICE guideline on type 2 diabetes is updated).

  • In EDITION 4 (n=549), once‑daily Toujeo was non‑inferior to once‑daily Lantus. A similar reduction in HbA1c from baseline to month 6 was seen in both treatment groups, with a difference between groups of 0.04% (0.4 mmol/mol), 95% CI −0.10 to 0.19% (−1.1 to 2.1 mmol/mol). This was below the pre‑specified non‑inferiority margin of 0.4%.

  • A similar proportion of participants in each treatment group achieved HbA1c below 7.0% (53 mmol/mol) at month 6; 16.8% with Toujeo and 15.0% with Lantus (no statistical analysis reported).

  • Rates of hypoglycaemia did not differ between treatment groups at 6 months. In the Toujeo group 93.1% of participants had 1 or more confirmed or severe hypoglycaemic event over 6 months compared with 93.5% of the Lantus group (relative risk [RR] 1.00; 95% CI 0.95 to 1.04). Nocturnal confirmed or severe hypoglycaemic events occurred in 68.6% of the Toujeo group and 70.2% of the Lantus group over 6 months (RR 0.98; 95% CI 0.88 to 1.09); and severe hypoglycaemic events in 6.6% of the Toujeo group and 9.5% of the Lantus group (RR 0.71; 95% CI 0.41 to 1.24).

  • At 6 months the basal insulin dose was approximately 18% higher with Toujeo (0.47 units/kg/day) than with Lantus (0.40 units/kg/day).

  • In EDITION 4, the number of participants with any adverse event or any serious adverse event was similar in the Toujeo and Lantus groups. Body weight increased with both Toujeo and Lantus, but at month 6 the mean increase was smaller with Toujeo (0.5 kg compared with 1.0 kg; p=0.037).

  • The EPAR states that the safety profile of Toujeo is largely similar to that of Lantus and no additional safety signals were detected. The most frequent adverse events were nasopharyngitis (8.2% with Toujeo, 6.8% with Lantus) and upper respiratory tract infection (6.5% with Toujeo, 5.8% with Lantus). Most of the adverse events were mild to moderate in intensity. Overall, serious adverse events were reported by 5.4% of people in both Toujeo and Lantus groups; most commonly hypoglycaemia in people with type 1 diabetes.

  • An important risk with high‑strength insulin glargine 300 units/ml (Toujeo) is possible medication errors with other insulins of lower strengths. Toujeo is not bioequivalent to insulin glargine 100 units/ml (Lantus) and dose adjustment is needed. However, the dose window of the Toujeo pen shows the number of Toujeo units to be injected.

  • The primary end point of the EDITION 4 trial (n=549) was HbA1c at 6 months. An extension study to 12 months has been completed, but not yet published. There are very limited patient‑oriented outcome data for the effects of Toujeo on macrovascular or microvascular outcomes, and very limited long‑term safety data for the 300 units/ml insulin glargine strength specifically.

Full text of Evidence review.

Context

Basal insulin supply for adults with type 1 diabetes can be provided by:

Toujeo (insulin glargine 300 units/ml) is the third insulin to be approved in Europe at a higher strength than the European Union‑wide standard of 100 units/ml. Insulin degludec (Tresiba) and insulin lispro (Humalog) are already available at a 200 units/ml strength.

The cost of Toujeo and other basal insulins will depend on the preparation chosen and the insulin dosage used.

Full text of Context.

Estimated impact for the NHS

High‑strength insulin products have been developed for people with large daily insulin requirements to reduce the number and volume of injections (MHRA Drug Safety Update April 2015).

In the main phase 3 study in people with type 1 diabetes (EDITION 4), Toujeo had similar efficacy to Lantus in terms of HbA1c reduction, with no difference in the risk of hypoglycaemia. The EPAR states that in people with type 1 diabetes the only advantage is the reduction in injection volume. However, specialists involved in the production of this evidence summary have suggested that large basal insulin requirements tend to be seen more in people with type 2 diabetes rather than type 1; and in EDITION 4 the mean injection volume at 6 months was calculated to be 0.1 ml (35 units) with Toujeo and 0.3 ml (30 units) with Lantus for a 75 kg adult. The EPAR states that the more gradual glucose lowering effect of Toujeo compared with Lantus did not translate into important advantages in people with type 1 diabetes, and the higher use of basal insulin may be a disadvantage. In order to obtain a similar effect on HbA1c, 18% higher doses of Toujeo than Lantus were needed in EDITION 4.

The European Medicines Agency has recently consulted on guidance to minimise the potential risk of medication errors associated with the availability of high‑strength insulins, such as Toujeo (MHRA Drug Safety Update April 2015).

Toujeo (insulin glargine 300 units/ml) is not simply interchangeable with other long‑acting insulins, including insulin glargine 100 units/ml. When switching between Toujeo and other basal insulins, different doses may be needed to achieve target ranges for plasma glucose levels, giving rise to a potential risk of medication error. This risk is addressed in advice given in the summary of product characteristics, and educational material for healthcare professionals and patients has been produced as an additional risk minimisation measure.

The updated NICE guideline on type 1 diabetes in adults: diagnosis and management recommends twice‑daily insulin detemir as the preferred basal insulin therapy. Other basal insulin regimens, including once‑daily insulin glargine can also be considered in certain circumstances. When choosing an alternative insulin regimen, the guideline recommends that the person's preferences and acquisition cost should be taken into account, and that people should have access to the insulin injection delivery device they find allows them optimal wellbeing. Toujeo was not considered specifically in the guideline because it was not available when the guideline was produced.

Full text of Estimated impact for the NHS.

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.