Xelevia - sitagliptina

What is Xelevia?

Xelevia is a medicine that contains the active substance sitagliptin. It is available as round tablets (pink: 25 mg; beige: 50 and 100 mg).

What is Xelevia used for?

Xelevia is used in patients with type 2 diabetes to improve the control of glucose (sugar) levels in the blood. It is used as follows, in addition to diet and exercise:

• in monotherapy, in patients who are not satisfactorily controlled with diet and exercise and in whom metformin (an antidiabetic medicine) is not suitable;

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

• in combination with a sulphonylurea (another type of antidiabetic medicine) in patients who are not satisfactorily controlled with the sulphonylurea alone 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 with these two medicines;

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

The medicine can only be obtained with a prescription.

How is Xelevia used?

Xelevia is taken at a dose of 100 mg once a day, with or without food. If Xelevia is taken in combination with a sulphonylurea or with insulin, it may be necessary to reduce the dose of the sulphonylurea or insulin to reduce the risk of hypoglycaemia (low blood sugar levels).

How does Xelevia work?

Type 2 diabetes is a disease in which the pancreas does not produce enough insulin to control the level of glucose in the blood or where the body is unable to use insulin effectively. The active substance in Xelevia, sitagliptin, is a dipeptidyl-peptidase-4 inhibitor (DPP-4). It works by inhibiting the degradation of "incretin" hormones in the body. These hormones, released after a meal, stimulate the pancreas to produce insulin. By increasing the level of incretin in the blood, sitagliptin 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. Sitagliptin also reduces the amount of glucose produced by the liver by increasing insulin levels and decreasing the levels of the glucagon hormone. Together, these processes reduce blood glucose and contribute to the control of type 2 diabetes.

How has Xelevia been studied?

Xelevia has been studied in nine studies involving nearly 6, 000 patients with type 2 diabetes whose blood glucose levels were not adequately controlled:

• in four of these studies Xelevia was compared with placebo (a dummy treatment): Xelevia or placebo were used alone in two studies involving 1 262 patients, in addition to metformin in a study involving 701 patients and in addition to pioglitazone (a PPAR gamma agonist) in a study of 353 patients;

• in two studies Xelevia was compared with other antidiabetic medicines. In the first study Xelevia was compared to glipizide (a sulphonylurea), when they were used in addition to metformin in 1 172 patients. In the second study, Xelevia was compared with metformin, used alone, in 1 058 patients;

• in three further studies Xelevia was compared with placebo when they were added to other antidiabetic medicines: a glimepiride (another sulphonylurea), with or without metformin, in 441 patients; to 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 the studies the main measure of effectiveness was the change in the blood concentration of a substance called glycosylated hemoglobin (HbA1c), which gives an indication of the effectiveness of blood glucose control.

What benefit has Xelevia shown during the studies?

Xelevia was more effective than placebo both as monotherapy and in combination with other antidiabetic medicines. In patients who took Xelevia alone, HbA1c levels decreased by 0.48% (from about 8.0% at the start of the studies) after 18 weeks and by 0.61% after 24 weeks. On the other hand, they increased by 0.12% and 0.18% respectively in patients taking placebo. The addition of Xelevia to metformin reduced HbA1c levels by 0.67% after 24 weeks, compared with a reduction of 0.02% in placebo-added patients. The addition of Xelevia to pioglitazone reduced HbA1c levels by 0.85% after 24 weeks, compared with a 0.15% reduction in placebo-added patients.

In studies in which Xelevia was compared to other medicines, the efficacy of adding Xelevia to metformin was similar to that of adding glipizide. When taken alone, Xelevia and metformin achieved similar reductions in HbA1c levels, but the effectiveness of Xelevia seemed to be slightly lower than that of metformin. In the other studies, when Xelevia was added to glimepiride (with or without metformin), HbA1c levels decreased by 0.45% after 24 weeks, compared with a 0.28% increase in placebo-added patients. HbA1c levels decreased by 1.03% after 18 weeks in patients adding Xelevia to metformin and rosiglitazone, against a decrease of 0.31% in those adding placebo; finally, they decreased by 0.59% in patients who added Xelevia to insulin (with or without metformin), compared to a 0.03% decrease in those adding placebo.

What is the risk associated with Xelevia?

Among the most common side effects reported with Xelevia (generally observed in more than 5% of patients) are upper respiratory tract infections (colds) and nasopharyngitis (inflammation of the nose and throat). For the full list of all side effects reported with Xelevia, see the Package Leaflet.

Xelevia should not be used in people who may be hypersensitive (allergic) to sitagliptin or any of the other ingredients.

Why has Xelevia been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Xelevia's benefits are greater than its risks and recommended that it be given marketing authorization.