o

EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/472049/2013

EMEA/H/C/002654

EPAR summary for the public

Vipdomet

alogliptin / metformin

This is a summary of the European public assessment report (EPAR) for Vipdomet. 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 Vipdomet.

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

What is Vipdomet and what is it used for?

Vipdomet is a diabetes medicine containing the active substances alogliptin and metformin. It is used as an addition to diet and exercise in adults with type-2 diabetes to improve the control of blood glucose (sugar) levels:

•    in patients who are not satisfactorily controlled with the maximum dose of metformin alone.

•    together with another diabetes medicine, pioglitazone, in patients who are not satisfactorily controlled with a combination of pioglitazone and metformin;

•    together with insulin, in patients who are not satisfactorily controlled with insulin and metformin.

Vipdomet can also be used as a replacement tablet (supplying both alogliptin and metformin) in patients who are already being treated with alogliptin and metformin given separately.

How is Vipdomet used?

Vipdomet is available as tablets (12.5 alogliptin and 850 or 1000 mg metformin) and can only be obtained with a prescription. It is taken by mouth twice daily. The choice of tablet strength to start with depends on the patient's current treatment. If patients were previously taking metformin alone, Vipdomet should be used at a strength that continues to provide the same dose of metformin. If patients are also taking pioglitazone or insulin, lower doses of these medicines may need to be given with Vipdomet to reduce the risk of hypoglycaemia (low blood sugar levels). For further information, see the summary of product characteristics (also part of the EPAR).

7 Westferry Circus • Canary Wharf • London E14 4HB • United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416 E-mail info@ema.europa.eu Website www.ema.europa.eu

© European Medicines Agency, 2013. Reproduction is authorised provided the source is acknowledged.

How does Vipdomet work?

Type-2 diabetes is a disease in which the pancreas does not make enough insulin to control the level of glucose in the blood or when the body is unable to use insulin effectively. The active substances in Vipdomet, alogliptin and metformin, work in different ways to help correct this.

Alogliptin is a dipeptidyl-peptidase-4 (DPP 4) inhibitor. It works by blocking the breakdown of 'incretin' hormones in the body. These hormones are released after a meal and stimulate the pancreas to produce insulin. By blocking the breakdown of incretin hormones in the blood, alogliptin prolongs their action in stimulating the pancreas to produce more insulin when blood glucose levels are high.

Alogliptin does not work when the blood glucose is low. Alogliptin also reduces the amount of glucose made by the liver, by increasing insulin levels and decreasing the levels of the hormone glucagon. Together, these processes reduce blood glucose levels and help to control type-2 diabetes. Alogliptin is licensed in the EU as Vipidia.

Metformin works mainly by inhibiting glucose production and reducing its absorption in the gut. Metformin has been available in the EU since the 1950s.

As a result of the action of both active substances, blood glucose levels are reduced and this helps to control the symptoms of type-2 diabetes.

What benefits of Vipdomet have been shown in studies?

Vipdomet has been studied in five main studies in patients with type-2 diabetes that was not well controlled by previous treatment. Three of the studies, involving 1,410 patients, compared the effects of alogliptin with placebo (a dummy treatment). Alogliptin was either used as an add-on to existing treatment with metformin (the same combination as in Vipdomet), pioglitazone (with or without metformin or another diabetes medicine), or insulin (with or without metformin). Two other studies involved 3,441 patients and compared the combination of alogliptin plus metformin with other treatments for diabetes (glipizide plus metformin or pioglitazone plus metformin). In all the studies, the main measure of effectiveness was the change in the level of glycosylated haemoglobin (HbA1c), which is the percentage of haemoglobin in the blood that has glucose attached. HbA1c levels give an indication of how well the blood glucose is controlled. HbA1c levels were measured after 26 weeks in the studies that compared alogliptin with placebo, and 52 weeks in the comparisons with other diabetes medicines.

All studies showed that alogliptin was effective when added to existing treatment and led to a decrease in the level of HbA1c, indicating that blood glucose levels had been reduced. After 26 weeks the fall in HbA1c with alogliptin and metformin was 0.48% more than with placebo and metformin. The combination of alogliptin plus metformin was at least as effective as pioglitazone plus metformin.

What are the risks associated with Vipdomet?

The most common side effects with Vipdomet (which may affect more than 1 in 10 people) are due to the metformin it contains and include abdominal pain (stomach ache), diarrhoea, loss of appetite, nausea (feeling sick) and vomiting. The commonest side effect due to alogliptin is pruritus (itching).

For the full list of all side effects reported with Vipdomet, see the package leaflet.

Vipdomet must not be used in patients who:

•    are hypersensitive (allergic) to the active substances or any of the ingredients or who have had serious allergic reactions to any dipeptidyl-peptidase-4 (DPP 4) inhibitor.

•    have diabetic ketoacidosis or pre-coma (a dangerous condition that can occur in diabetes)

Vipdomet

EMA/472049/2013    Page 2/3

•    have moderately to severely reduced kidney function or are suffering from acute (short-term) conditions which can affect kidney function such as dehydration

•    suffer from acute or chronic diseases which can cause tissue hypoxia (where the tissue is deprived of adequate oxygen supply) such as heart failure, respiratory failure (inability to take in enough oxygen or breathe out enough carbon dioxide), heart attack or shock

•    have reduced liver function or suffer from alcohol poisoning or alcoholism.

For the full list of restrictions, see the package leaflet.

Why is Vipdomet approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that Vipdomet's benefits are greater than its risks and recommended that it be approved for use in the EU. The studies showed that adding alogliptin to existing treatment with metformin (with or without pioglitazone) or to insulin produced modest but clinically relevant improvements. The CHMP therefore considered that the combination of alogliptin and metformin in Vipdomet is of benefit to patients. Regarding safety, Vipdomet, did not seem to be associated with weight gain which is a known side effect of most diabetes medicines and the safety profile was consistent with that seen with the individual components.

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

A risk management plan has been developed to ensure that Vipdomet 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 Vipdomet, including the appropriate precautions to be followed by healthcare professionals and patients.

Other information about Vipdomet

The European Commission granted a marketing authorisation valid throughout the European Union for Vipdomet on 19 September 2013.

The full EPAR for Vipdomet 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 Vipdomet, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 08-2013.

Vipdomet

EMA/472049/2013