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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/790269/2014

EMEA/H/C/001234

EPAR summary for the public

Ristaben

sitagliptin

This is a summary of the European Public Assessment Report (EPAR) for Ristaben. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Ristaben.

What is Ristaben?

Ristaben is a diabetes medicine that contains the active substance sitagliptin. It is available as tablets

(25, 50 and 100 mg).

What is Ristaben used for?

Ristaben is used in patients with type 2 diabetes to improve the control of blood glucose (sugar) levels.

It is used in addition to diet and exercise in the following ways:

•    on its own, in patients who are not satisfactorily controlled on diet and exercise and in whom metformin (a diabetes medicine) is not suitable;

•    in combination with metformin or a PPAR-gamma agonist (a type of diabetes medicine) such as a thiazolidinedione, in patients who are not satisfactorily controlled on metformin or the PPAR-gamma agonist used on its own;

•    in combination with a sulphonylurea (another type of diabetes medicine) in patients who are not satisfactorily controlled with a sulphonylurea used on its own and in whom metformin is not suitable;

•    in combination with both metformin, and a sulphonylurea or a PPAR-gamma agonist, in patients who are not satisfactorily controlled on the two medicines;

•    in combination with insulin, with or without metformin, in patients who are not satisfactorily controlled on a stable dose of insulin.

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The medicine can only be obtained with a prescription.

How is Ristaben used?

Ristaben is taken at a dose of 100 mg once a day. If Ristaben is taken with a sulphonylurea or insulin, the dose of the sulphonylurea or insulin may need to be lowered to reduce the risk of hypoglycaemia (low blood sugar levels).

In patients with moderately or severely reduced kidney function the dose of Ristaben should be reduced.

How does Ristaben 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 substance in Ristaben, sitagliptin, 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, sitagliptin stimulates the pancreas to produce more insulin when blood glucose levels are high. Sitagliptin does not work when the blood glucose is low. Sitagliptin 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.

How has Ristaben been studied?

Ristaben was studied in nine studies involving almost 6,000 patients with type 2 diabetes whose blood glucose levels were not adequately controlled:

•    four of the studies compared Ristaben with placebo (a dummy treatment). Ristaben or placebo were used on their own in two studies involving 1,262 patients, as an add-on to metformin in one study involving 701 patients, and as an add-on to pioglitazone (a PPAR-gamma agonist) in one study involving 353 patients;

•    two studies compared Ristaben with other diabetes medicines. One study compared Ristaben with glipizide (a sulphonylurea), when they were used as an add-on to metformin in 1,172 patients. The other study compared Ristaben with metformin, used on their own, in 1,058 patients;

•    three additional studies compared Ristaben with placebo when they were added to other diabetes medicines: glimepiride (another sulphonylurea), with or without metformin, in 441 patients; the combination of metformin and rosiglitazone (a PPAR-gamma agonist) in 278 patients; and a stable dose of insulin, with or without metformin, in 641 patients.

In all of the studies, the main measure of effectiveness was the change 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.

What benefit has Ristaben shown during the studies?

Ristaben was more effective than placebo when it was taken alone or in combination with other diabetes medicines. In patients taking Ristaben on its own, HbA1c levels fell from around 8.0% at the start of the studies by 0.48% after 18 weeks and 0.61% after 24 weeks. In contrast, they rose by 0.12% and 0.18%, respectively, in the patients taking placebo. Adding Ristaben to metformin reduced

HbAlc levels by 0.67% after 24 weeks, compared with a fall of 0.02% in the patients adding placebo. When added to pioglitazone, Ristaben reduced HbAlc levels by 0.85% after 24 weeks, compared with a fall of 0.15% in the patients adding placebo.

In the studies comparing Ristaben with other medicines, the effectiveness of adding Ristaben to metformin was similar to that of adding glipizide. When taken on their own, Ristaben and metformin produced similar reductions in HbAlc levels, but the effectiveness of Ristaben seemed to be slightly lower than that of metformin.

In the additional studies, adding Ristaben to glimepiride (with or without metformin) led to a reduction in HbAlc levels of 0.45% after 24 weeks, compared with an increase of 0.28% in the patients adding placebo. HbAlc levels were reduced by 1.03% after 18 weeks in patients adding Ristaben to metformin and rosiglitazone, compared with a fall of 0.3l% in those adding placebo. Finally, they were reduced by 0.59% in patients adding Ristaben to insulin (with or without metformin), compared with a fall of 0.03% in those adding placebo.

What is the risk associated with Ristaben?

Serious side effects reported with Ristaben include pancreatitis (inflammation of the pancreas) and hypersensitivity (allergic reactions). Hypoglycaemia has been reported in combination with a sulphonylurea in 4.7-l3.8% of patients and with insulin in 9.6% of patients. For the full list of all side effects and restrictions with Ristaben, see the package leaflet.

Why has Ristaben been approved?

The CHMP decided that Ristaben's benefits are greater than its risks and recommended that it be given marketing authorisation.

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

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

Other information about Ristaben:

The European Commission granted a marketing authorisation valid throughout the European Union for Ristaben on l5 March 20l0. This authorisation was based on the authorisation granted to Januvia in 2007 ('informed consent').

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

This summary was last updated in 0l-20l5.

Ristaben

EMA/790269/2014

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