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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/383096/2015

EMEA/H/C/002647

EPAR summary for the public

Xultophy

insulin degludec / liraglutide

This is a summary of the European public assessment report (EPAR) for Xultophy. It explains how the Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is not intended to provide practical advice on how to use Xultophy.

For practical information about using Xultophy, patients should read the package leaflet or contact their doctor or pharmacist.

What is Xultophy and what is it used for?

Xultophy is a medicine that is used for the treatment of type 2 diabetes. It is used together with diabetes medicines taken by mouth in adults whose blood glucose (sugar) levels are not satisfactorily controlled by these medicines alone or combined with either a diabetes medicine called GLP-1 agonist or insulin.

The active substances in Xultophy are insulin degludec and liraglutide.

How is Xultophy used?

Xultophy is available as pre-filled disposable pens and can only be obtained with a prescription. It is given as an injection under the skin of the thigh, the upper arm or the abdomen (belly). The site of injection should be changed with each injection to avoid changes to the skin (such as thickening) that can make the medicine work less well than expected. Patients can inject themselves with Xultophy if they have been trained appropriately.

Xultophy is given once a day, preferably at the same time each day. The dose is adjusted individually for each patient, and the patient's blood glucose should be regularly tested to find the lowest effective dose.

For further information, see the package leaflet.

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How does Xultophy work?

Type 2 diabetes is a disease in which the body does not produce enough insulin to control the level of blood glucose, or the body is unable to use insulin effectively. One of the active substances in Xultophy, insulin degludec, is a replacement insulin that acts in the same way as naturally produced insulin and helps glucose enter cells from the blood. By controlling the level of blood glucose, the symptoms and complications of diabetes are reduced. Insulin degludec is slightly different from human insulin as it is absorbed more slowly and regularly by the body after an injection and it has a long duration of action.

The other active substance in Xultophy, liraglutide, belongs to the class of diabetes medicines known as GLP-1 agonists. It acts in the same way as incretins (hormones produced in the gut) by increasing the amount of insulin that the pancreas releases in response to food. This helps with the control of blood glucose levels.

What benefits of Xultophy have been shown in studies?

Once-daily injection of Xultophy has been shown to be of benefit in controlling blood glucose in three main studies involving 2,514 patients with type 2 diabetes. In all studies, the main measure of effectiveness was the change after 6 months of treatment in the level in the blood of a substance called glycosylated haemoglobin (HbA1c), which gives an indication of how well blood glucose is controlled.

•    The first study involved 1,663 patients whose diabetes was not adequately controlled with the diabetes medicines metformin or metformin and pioglitazone taken by mouth; adding Xultophy to their treatment was compared with adding either of its active substances, insulin degludec or liraglutide. The average HbA1c level, which was 8.3% at the start, fell to 6.4% after 26 weeks of treatment with Xultophy, compared with 6.9% and 7.0% respectively with insulin degludec and liraglutide.

•    The second study involved 413 patients whose blood glucose was not adequately controlled by insulin and metformin with or without other diabetes medicines taken by mouth. Treatment with Xultophy and metformin was compared with treatment using insulin degludec and metformin. Average HbA1c at the start was 8.7% in the Xultophy group, and fell after 26 weeks of treatment to 6.9%. In the group using insulin degludec it fell from 8.8% to 8.0%.

•    The third study involved 438 patients whose blood glucose was not adequately controlled by a combination of a GLP-1 agonist (liraglutide or exenatide) and metformin with or without other diabetes medicines taken by mouth. Patients in the study either continued with their current treatment or received Xultophy instead of the GLP-1 agonist. Average HbA1c was 7.8% before patients started to receive Xultophy, and fell after 26 weeks of treatment to 6.4%. In the group that kept on receiving the GLP-1 agonist, it fell from 7.7% to 7.4%.

The majority of patients treated with Xultophy in these studies achieved control of their blood glucose (HbA1c below 7.0%) and many achieved HbA1c below 6.5%.

What are the risks associated with Xultophy?

The most common side effect with Xultophy (which may affect more than 1 in 10 people) is hypoglycaemia (low blood glucose). Side effects on the digestive system occurred in up to 1 in 10 patients and included nausea (feeling sick), diarrhoea, vomiting, constipation, dyspepsia (indigestion), gastritis (inflammation of the stomach), abdominal pain (stomach ache), flatulence (wind), gastroesophageal reflux disease (passage of stomach acid back up towards the mouth), and distension

Xultophy

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(swelling) of the belly. For the full list of all side effects and restrictions with Xultophy, see the package leaflet.

Why is Xultophy approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Xultophy's benefits are greater than its risks and recommended that it be approved for use in the EU. The Committee considered that adding this medicine to other diabetes medicines offers better control of blood glucose and having an alternative treatment option is valuable in individualising treatment.

What measures are being taken to ensure the safe and effective use of Xultophy?

A risk management plan has been developed to ensure that Xultophy is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Xultophy, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that markets Xultophy will provide educational materials for healthcare professionals, explaining how to use the medicine safely, so as to reduce the risk of medication errors.

Further information can be found in the summary of the risk management plan.

Other information about Xultophy

The European Commission granted a marketing authorisation valid throughout the European Union for Xultophy on 18 September 2014.

The full EPAR and risk management plan summary for Xultophy can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports. For more information about treatment with Xultophy, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 06-2015.

Xultophy

EMA/383096/2015