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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/748774/2015

EMEA/H/C/003770

EPAR summary for the public

Synjardy

empagliflozin / metformin

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

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

What is Synjardy and what is it used for?

Synjardy is a diabetes medicine that is used, in combination with diet and exercise, in adults with type 2 diabetes to improve the control of their blood glucose (sugar) levels. It contains two active substances, empagliflozin and metformin.

Synjardy is used in the following groups:

•    patients whose blood glucose levels are not satisfactorily controlled by the maximum tolerated dose of metformin alone;

•    patients taking metformin as an add-on to other diabetes medicines, including insulin, when combinations of these with metformin alone are insufficient;

•    patients who are already taking metformin and empagliflozin as separate tablets.

How is Synjardy used?

Synjardy is available as tablets containing 5 or 12.5 mg of empagliflozin with 850 or 1000 mg of metformin, and can only be obtained with a prescription. The recommended dose is one tablet twice a day, and treatment is normally started with a tablet that supplies the dose of metformin the patient is

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already taking, together with the lowest dose (5 mg) of empagliflozin. Doses are adjusted as necessary.

If Synjardy is used in combination with insulin or medicines that make the body produce insulin, their doses may need to be reduced to decrease the risk of hypoglycaemia (low blood sugar levels). Treatment with this medicine is not recommended in some patients, such as those aged above 85 years or with moderately or severely impaired kidney function. For further information, see the package leaflet.

How does Synjardy work?

Type 2 diabetes is a disease in which the body 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 result is a high level of glucose in the blood. The two active substances in Synjardy work in different ways to lower this, and thus to control symptoms of the disease.

Empagliflozin works by blocking a protein in the kidneys (called sodium-glucose co-transporter 2 or SGLT2), which normally absorbs glucose back from the urine into the bloodstream. By blocking the action of this protein, empagliflozin causes more glucose to be removed via the urine, thereby reducing the levels of glucose in the blood. Empagliflozin has been authorised in the EU under the trade name Jardiance since 2014.

The active substance metformin works mainly by blocking glucose production in the liver and reducing its absorption in the gut. Metformin has been available in the EU since the 1950s.

What benefits of Synjardy have been shown in studies?

The benefits of empagliflozin in combination with metformin have been shown in 3 main studies involving 1,679 patients with type 2 diabetes whose blood sugar was not adequately controlled by metformin, alone or combined with other diabetes medicines (such as pioglitazone or a type of diabetes medicine called a sulphonylurea). The studies compared the effect of empagliflozin plus metformin versus placebo (a dummy treatment) with metformin. The main measure of effectiveness was the change in the level of a substance in the blood called glycosylated haemoglobin (HbAlc), which gives an indication of how well the blood glucose is controlled, after 24 weeks of treatment.

The studies showed a greater reduction in HbAlc when empagliflozin plus metformin was given, compared with placebo plus metformin. Overall, the additional reduction was 0.58 percentage points with a combination providing 5 mg of empagliflozin twice daily, and 0.62 percentage points with the 12.5 mg dose, and these reductions were considered clinically relevant. Similar benefits were seen in the studies regardless of the other diabetes medicines being taken. In addition, the results indicated that the combination was associated with a beneficial decrease in body weight and blood pressure.

Supportive evidence was provided from several further studies. Some of these were continuations of the main studies that suggested the benefits of the combination continued with longer therapy. Studies also indicated Synjardy was as effective as empagliflozin and metformin taken separately, and that the combination helped reduce HbA1c when added to treatment including insulin.

What are the risks associated with Synjardy?

The most common side effects with Synjardy are hypoglycaemia (low blood sugar levels) when the medicine is taken with a sulphonylurea or insulin, infections of the urinary tract or genitals, and increased urination. For the full list of all side effects reported with Synjardy, see the package leaflet.

Synjardy must not be used in patients with:

•    diabetic ketoacidosis or diabetic pre-coma (dangerous complications of diabetes);

•    moderately or severely reduced kidney function or with rapidly developing conditions that could affect the kidneys such as dehydration, severe infection or shock;

•    a condition that could lead to reduced supply of oxygen to body tissues (such as in patients who are being treated for worsening heart failure, have recently had a heart attack, have breathing problems or a steep fall in blood pressure);

•    liver impairment, or problems with alcoholism or alcohol intoxication.

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

Why is Synjardy approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Synjardy's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP concluded that the medicine could help produce a clinically meaningful reduction in blood glucose in patients with type 2 diabetes, and the benefits and risks were in line with those of the individual active substances. There were some concerns about the balance of benefit and risk in patients with reduced kidney function taking the fixed dose combination, and the CHMP recommended restricting its use in these patients.

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

A risk management plan has been developed to ensure that Synjardy 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 Synjardy, 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 Synjardy

The European Commission granted a marketing authorisation valid throughout the European Union for Synjardy on 27 May 2015.

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

This summary was last updated in 11-2015.

Synjardy

EMA/748774/2015

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