Eucreas - vildagliptin and metformin hydrochloride

What is Eucreas?

Eucreas is a drug containing the active substances vildagliptin and metformin hydrochloride. It is available as oval tablets (dark yellow: 50 mg / 850 mg; light yellow: 50 mg / 1 000 mg).

What is Eucreas used for?

Eucreas is used to treat type 2 diabetes (non-insulin-dependent diabetes). It is used in patients whose disease is insufficiently controlled at the maximum tolerated dose of metformin taken alone or who are already taking the combination of vildagliptin and metformin given as separate tablets.

The medicine can only be obtained with a prescription.

How is Eucreas used?

The recommended dose of Eucreas is one tablet twice a day, one tablet in the morning and one in the evening. The choice of the initial dose depends on the dose of metformin currently taken by the patient, but the recommended dose is 50 mg of vildagliptin and 1 000 mg of metformin twice a day. Patients already taking vildagliptin and metformin should switch to Eucreas tablets containing the same doses of each active ingredient. Doses higher than 100 mg vildagliptin are not recommended. Taking Eucreas during or immediately after meals may reduce stomach problems caused by metformin.

Eucreas should not be used by patients with moderate to severe renal insufficiency or with liver disorders. In older patients taking Eucreas, renal function should be monitored regularly. Eucreas is not recommended for patients over 75 years of age.

How does Eucreas work?

Type 2 diabetes is a disease due to the fact that the pancreas does not produce enough insulin to control the level of glucose (sugar) in the blood or when the body is unable to use insulin effectively. Eucreas contains two active ingredients that each perform a different action. Vildagliptin, a dipeptidyl-peptidase 4 (DPP-4) inhibitor, works by inhibiting the degradation of "incretin" hormones in the body. Incretins, which are released into the blood after a meal, stimulate the pancreas to produce insulin. By increasing the level of incretin in the blood, vildagliptin stimulates the pancreas to produce more insulin when the glycemic rate is high, while it is ineffective when the concentration of glucose in the blood is low. Vildagliptin also reduces the amount of glucose produced by the liver by increasing insulin levels and decreasing the levels of the glucagon hormone. Metformin basically inhibits glucose production and reduces

its absorption in the intestine. The result of the combined action of the two active ingredients consists in a reduction of the glucose present in the blood, which helps to control type 2 diabetes.

What studies have been carried out on Eucreas?

In September 2007, Vildagliptin alone was approved by the Union eueropea (EU) under the name Galvus, while metformin has been available in the EU since 1959. Vildagliptin can be used with metformin in patients with type 2 diabetes, whose disease is not sufficiently controlled with metformin alone. Studies on Galvus have been integrated with those on metformin to support the use of Eucreas for the same indication. In these studies the level of a substance called glycosylated hemoglobin (HbA1c) in the blood was measured, which gives an indication of the effectiveness of blood glucose control.

The applicant also presented the results of two studies showing that the active ingredients in the two dosages of Eucreas are absorbed by the body in the same way as when they are taken as separate tablets.

What benefit has Eucreas shown during the studies?

Vildagliptin was more effective than placebo (phytopic treatment) in reducing HbA1c levels when added to metformin. Patients who added vildagliptin reported a decrease in HbA1c levels of 0.88% after 24 weeks, with an initial level of 8.38%. Instead, patients who added the placebo recorded minor changes in HbA1c levels, with an increase of 0.23%, starting at an initial level of 8.30%.

What is the risk associated with Eucreas?

The most common side effects recorded with Eucreas (seen in more than 1 patient in 10) are nausea, vomiting, diarrhea, abdominal pain and loss of appetite. For the full list of all side effects reported with Eucreas, see the Package Leaflet.

Eucreas should not be used in people who may be hypersensitive (allergic) to vildagliptin, metformin or any of the other ingredients (components). It must not be used in patients with diabetic ketoacidosis (high levels of ketones and acids in the blood), diabetic pre-coma, kidney or liver problems, conditions that may affect the kidneys or a disease that causes a reduced supply of oxygen to the tissues such as heart or lung failure or a recent heart attack. Also, it should not be used in patients with alcohol intoxication (excessive alcohol consumption) or alcoholism in breastfeeding. For the full list of limitations, see the package leaflet.

Why has Eucreas been approved?

The Committee for Medicinal Products for Human Use (CHMP) concluded that vildagliptin taken with metformin reduces blood glucose levels and that the combination of the two active substances in a tablet can help patients stick to their treatment.

The Committee therefore decided that Eucreas's benefits outweigh the risks in the treatment of patients with type 2 diabetes mellitus, who are unable to achieve sufficient glycemic control at their maximum tolerated dose of oral metformin or who are already treated with the combination of vildagliptin and metformin in separate capsules. The Committee recommended that Eucreas be given marketing authorization.