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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/378777/2016

EMEA/H/C/004057

EPAR summary for the public

Qtern

saxagliptin / dapagliflozin

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

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

What is Qtern and what is it used for?

Qtern is used to treat adults with type 2 diabetes to improve control of their blood glucose (sugar) levels. It contains the active substances saxagliptin and dapagliflozin.

Qtern is used in patients whose blood glucose levels are not satisfactorily controlled with:

•    metformin and one of the components of Qtern;

•    a sulphonylurea and one of the components of Qtern;

•    metformin, a sulphonylurea and one of the components of Qtern.

Qtern can also be used to replace saxagliptin and dapagliflozin taken as separate tablets.

How is Qtern used?

Qtern is available as tablets (5 mg saxagliptin and 10 mg dapagliflozin) and can only be obtained with a prescription. The recommended dose is one tablet taken once a day. For further information, see the package leaflet.

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© European Medicines Agency, 2016. Reproduction is authorised provided the source is acknowledged.

How does Qtern work?

Type 2 diabetes is a disease in which the pancreas does not make enough insulin to control the levels of glucose in the blood or when the body is unable to respond to insulin effectively. This leads to high levels of glucose in the blood.

Qtern contains two different active substances, which work in different ways:

•    dapagliflozin works by blocking a protein in the kidneys called sodium-glucose co-transporter 2 (SGLT2). As blood is filtered by the kidneys, SGLT2 stops glucose in the bloodstream from being passed out into the urine. By blocking the action of SGLT2, dapagliflozin causes more glucose to be removed via the kidney, through the urine, thereby reducing the levels of glucose in the blood. Dapagliflozin has been authorised in the European Union (EU) as Forxiga since 2012;

•    saxagliptin, 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 increasing levels of incretin hormones in the blood, saxagliptin stimulates the pancreas to produce more insulin when blood glucose levels are high. Saxagliptin does not work when the blood glucose is low. Saxagliptin also reduces the amount of glucose made by the liver, by increasing insulin levels and decreasing the levels of the hormone glucagon. Saxagliptin has been authorised in the EU as Onglyza since 2009.

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

What benefits of Qtern have been shown in studies?

Dapagliflozin in combination with saxagliptin (the same combination as in Qtern) was evaluated in 3 main studies involving 1,169 adults with type 2 diabetes. The main measure of effectiveness was the change after 24 weeks of treatment in the level of a substance in the blood called glycosylated haemoglobin (HbA1c), which gives an indication of how well the blood glucose is controlled.

The first study included patients whose blood glucose levels were not satisfactorily controlled with metformin alone. Results showed that when saxagliptin and dapagliflozin were taken together with metformin, they decreased HbA1c levels by 1.5 percentage points after 24 weeks, compared with a reduction of 0.9 percentage points with saxagliptin and metformin and 1.2 percentage points with dapagliflozin and metformin. HbA1c levels were on average around 9% at the start of the study.

The second study included patients whose blood glucose levels were not satisfactorily controlled with metformin and dapagliflozin. Results showed that adding saxagliptin to treatment with dapagliflozin and metformin for 24 weeks reduced HbA1c levels by 0.5 percentage points, compared with a reduction of 0.2 percentage points when placebo (a dummy treatment) was added to treatment with dapagliflozin and metformin. HbA1c levels were around 8% at the start of the study.

A further study, which included patients not controlled with metformin and saxagliptin, showed that adding dapagliflozin to treatment with saxagliptin and metformin for 24 weeks reduced HbA1c levels by 0.8 percentage points, compared with a reduction of 0.1 percentage points when placebo was added to saxagliptin and metformin.

The company also provided studies that were used in the authorisation of Forxiga and Onglyza where saxagliptin or dapagliflozin were used together with a sulphonylurea.

What are the risks associated with Qtern?

The most common side effects with Qtern (which may affect more than 1 in 10 people) are upper respiratory tract infection (such as nose and throat infections) and, when used with a sulphonylurea, hypoglycaemia (low blood glucose levels). For the full list of all side effects reported with Qtern, see the package leaflet.

Qtern must not be used in people who are hypersensitive (allergic) to saxagliptin, dapagliflozin, any of the other ingredients or who have ever had a serious allergic reaction to any DPP-4 or SGLT2 inhibitor.

Why is Qtern approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Qtern's benefits are greater than its risks and recommended that it be approved for use in the EU.

The CHMP concluded that Qtern is effective when using it to replace saxagliptin and dapagliflozin taken as separate tablets. The CHMP also considered Qtern to be effective at controlling blood glucose levels when used in patients who were not satisfactorily controlled with metformin plus either saxagliptin or dapagliflozin. Although both components of Qtern contribute to lowering blood glucose levels, the effects of each may vary in different patients. The CHMP therefore considered that Qtern should only be used in patients already receiving at least one component to avoid over-treatment and so that the value of each component can be judged individually.

On the basis of previous studies with the individual components of Qtern used together with a sulphonylurea, the CHMP also approved the combination of Qtern with a sulphonylurea.

Regarding its safety profile, Qtern was well tolerated with side effects being characteristic of SGLT2 and DDP-4 inhibitors.

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

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Qtern have been included in the summary of product characteristics and the package leaflet.

Other information about Qtern

The European Commission granted a marketing authorisation valid throughout the European Union for Qtern on 15 July 2016.

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

This summary was last updated in 07-2016.

Qtern

EMA/378777/2016

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