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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/764090/2015

EMEA/H/C/004162

EPAR summary for the public

Ebymect

dapagliflozin / metformin

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

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

What is Ebymect and what is it used for?

Ebymect is a diabetes medicine that contains the active substances dapagliflozin and metformin. It is used, together with diet and exercise, to control the blood glucose (sugar) levels in adults with type 2 diabetes whose disease is not satisfactorily controlled with metformin alone, or in combination with other diabetes medicines, including insulin, when these medicines together with metformin are not providing adequate control of the diabetes. Ebymect can also be used to replace dapagliflozin and metformin taken as separate tablets.

This medicine is the same as Xigduo, which is already authorised in the European Union (EU). The company that makes Xigduo has agreed that its scientific data can be used for Ebymect ('informed consent').

How is Ebymect used?

Ebymect is available as tablets (5 mg dapagliflozin/850 mg metformin and 5 mg dapagliflozin/

1,000 mg metformin) and can only be obtained with a prescription.

The recommended dose is one tablet taken twice a day with a meal; the strength should be chosen so that in total, patients receive 10 mg of dapagliflozin each day and the same dose (or as close as possible to it) of metformin they were already taking before starting Ebymect. When Ebymect is used with insulin, the doctor may need to lower the dose of insulin to reduce the risk of hypoglycaemia (low blood sugar levels).

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How does Ebymect 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 use insulin effectively. This leads to high levels of glucose in the blood.

Ebymect 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). SGLT2 absorbs glucose from the urine into the bloodstream as the blood is filtered in the kidneys. By blocking the action of SGLT2, dapagliflozin causes more glucose to be removed via the urine, thereby reducing the levels of glucose in the blood. Dapagliflozin has been authorised in the European Union (EU) as Forxiga since 2012;

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

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 Ebymect have been shown in studies?

Dapagliflozin in combination with metformin was evaluated in 6 main studies involving 3,200 adults with type 2 diabetes. The majority of these data had already been used in the authorisation of Forxiga.

In one main study, when dapagliflozin was used at a dose of 5 mg twice a day in addition to metformin (the same combination as in Ebymect), it decreased HbA_1c (glycosylated haemoglobin) levels by 0.65% after 16 weeks, compared with a reduction of 0.30% with placebo (a dummy treatment) and metformin. HbA_1c is a substance in the blood which gives an indication of how well the blood glucose is controlled. Two other studies showed that dapagliflozin taken with metformin and another diabetes medicine, sitagliptin or insulin, for 24 weeks, further decreased HbA_1c: the dapagliflozin combination decreased HbA_1c levels by 0.40% more than placebo and metformin when added to sitagliptin, and by 0.61% more than placebo and metformin when added to insulin. Further studies confirmed that different doses of dapagliflozin with metformin decreased HbA_1c more than placebo plus comparable doses of metformin, and that dapagliflozin plus metformin was at least as effective in reducing HbA1c levels as the diabetes medicine glipizide (a type of medicine known as a sulphonylurea). One study showed that after 24 weeks of treatment, patients taking dapagliflozin plus metformin had an average reduction in body weight of around 2 kg more than those taking placebo plus metformin.

What are the risks associated with Ebymect?

The most common side effects with Ebymect (which may affect more than 1 in 10 people) are hypoglycaemia (when used together with insulin or a sulphonylurea) and gastrointestinal symptoms (symptoms affecting the stomach and gut). For the full list of all side effects reported with Ebymect, see the package leaflet.

Ebymect must not be used in:

•    patients with diabetic ketoacidosis (high blood levels of acids called 'ketones') or diabetic pre-coma (a dangerous condition that can occur in diabetes);

•    patients with reduced liver function;

•    patients with moderate or severe reduction in kidney function or with acute conditions that could potentially alter kidney function such as dehydration, severe infection or shock;

Ebymect

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•    patients with diseases that could cause tissue hypoxia (reduced levels of oxygen in body tissues);

•    patients with alcoholism.

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

Why is Ebymect approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Ebymect's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP considered Ebymect to be effective at controlling blood glucose levels; it also leads to weight loss, which is considered beneficial in patients with diabetes. The CHMP also noted that giving the combination of dapagliflozin and metformin as a single tablet could provide an additional treatment option for patients with type 2 diabetes, and may improve adherence to treatment. Regarding its safety profile, this was considered similar to the safety profile of dapagliflozin.

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

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

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

Other information about Ebymect

The European Commission granted a marketing authorisation valid throughout the European Union for Ebymect on 16 November 2015.

The full EPAR and risk management plan summary for Ebymect 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 Ebymect, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 11-2015.

Ebymect

EMA/764090/2015