Ebymect - Dapagliflozin Metformin

What is Ebymect and what is it used for - Dapagliflozin Metformin?

Ebymect is a medicine containing the active substances dapagliflozin and metformin. It is indicated, in addition to diet and exercise, to control blood glucose (sugar) levels in adult patients with type 2 diabetes mellitus inadequately controlled with metformin taken alone; it is also indicated in combination with other antidiabetic medicines, including insulin, when these medicines, in combination with metformin, do not provide adequate diabetes control. Ebymect can also be used to replace dapagliflozin and metformin taken as separate tablets.

This medicine is the same as Xigduo, already authorized 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 - Dapagliflozin Metformin?

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 twice a day, during meals. The dosage should be chosen so that patients receive a total daily dose of medicine equivalent to 10 mg dapagliflozin in addition to the dose of metformin (or the nearest therapeutically appropriate dose) already administered. When Ebymect is used in combination with insulin, your doctor may decide to lower your insulin dose to reduce the risk of hypoglycaemia (low blood glucose concentration).

How does Ebymect - Dapagliflozin Metformin work?

Type 2 diabetes is a disease in which the pancreas does not produce enough insulin to control blood glucose levels or where the body is unable to use insulin effectively, which leads to increased levels of glucose in the blood. Ebymect contains two different active ingredients, each with a different mechanism of action:

dapagliflozin works by blocking a protein in the kidneys, called type 2 sodium glucose transporter (SGLT2). SGLT2 is a protein responsible for the reabsorption of glucose into the bloodstream (bloodstream) from urine, when blood is filtered through the kidneys. By blocking the action of SGLT2, dapagliflozin induces the elimination of more glucose through the urine and, consequently, the reduction of the concentration of glucose in the blood. Dapagliflozin was authorized in the European Union (EU) as Forxiga in 2012;
Metformin acts mainly by inhibiting the production of glucose and reducing its absorption in the intestine. It has been available in the EU since the 1950s.

Thanks to the combined action of the two active ingredients, the rate of glucose in the blood is reduced and this serves to control type 2 diabetes.

What benefit has Ebymect - Dapagliflozin Metformin shown during the studies?

Dapagliflozin, in combination with metformin, was evaluated in 6 main studies involving 3 200 adults with type 2 diabetes. Most of this data had already been used in Forxiga's application for authorization.

In a main study in which it was used at a dose of 5 mg twice a day in combination with metformin (in the same combination as Xigduo), dapagliflozin decreased HbA1c levels by 0.65% compared to 0.30% observed in group treated with placebo (a dummy treatment) and metformin after 16 weeks. HbA1c (glycosylated hemoglobin) is a substance present in the blood that gives an indication of the effectiveness of blood glucose control. Two other studies showed that dapagliflozin taken with metformin and another antidiabetic medicine (sitagliptin or insulin) for 24 weeks further reduced HbA1c levels: compared to the combination of placebo and metformin, the combination of dapagliflozin and metformin induced a reduction in HbA1c levels of 0.40% higher if associated with sitagliptin, and 0.61% higher when combined with insulin. Further studies confirmed that different combinations of dapagliflozin and metformin decreased HbA1c levels more than the combinations of placebo and comparable metformin doses, and that the combination of dapagliflozin and metformin compared to the antidiabetic drug glipizide (a type of medicine known as sulfonylurea) demonstrated at least equal efficacy in reducing HbA1c levels. As part of a sixth study it was found that, after 24 weeks of treatment, a weight loss of about 2 kg more was observed in patients receiving dapagliflozin associated with metformin compared to subjects treated with placebo and metformin.

What is the risk associated with Ebymect - Dapagliflozin Metformin?

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

Ebymect is contraindicated in patients with:

diabetic ketoacidosis (increase in blood levels of a type of acid called "ketones") or diabetic pre-coma (a dangerous condition that can occur in diabetic subjects);
reduced liver function;
moderate or severe changes in renal function or acute conditions that could alter renal function, including dehydration, severe infection or shock;
diseases that can cause tissue hypoxia (decreased oxygen levels in body tissues);
alcoholism.

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

Why has Ebymect - Dapagliflozin Metformin been 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 noted that Ebymect is effective in controlling blood glucose levels and that it also induces weight loss, which is considered an advantage in diabetic patients. The CHMP also noted that administering the combination of dapagliflozin and metformin in a single tablet could be an additional therapeutic option for individuals with type 2 diabetes and improve adherence to therapy. As for the safety profile, it was considered similar to the safety profile of dapagliflozin.

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

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.