What is Ristaben?
Ristaben is a medicine that contains the active substance sitagliptin and is available as round tablets (25 mg pink, 50 and 100 mg beige).
The medicine is identical to Januvia, already authorized in the European Union (EU). The manufacturer of Januvia has agreed that the scientific data related to it are also used for Ristaben ("informed consent").
What is Ristaben used for?
Ristaben is used in patients with type 2 diabetes to improve the control of glucose (sugar) in the blood, as a complement to a diet and exercise, in the following ways:
• on its own in patients in whom diet and exercise do not allow for sufficient control and are not suitable for treatment with metformin (an antidiabetic);
• in combination with metformin or a PPAR-gamma agonist (antidiabetic type) such as thiazolidinedione in patients insufficiently controlled with metformin or the PPAR-gamma agonist alone;
• in combination with a sulphonylurea (another type of antidiabetic) in patients insufficiently controlled with sulphonylurea alone and not suitable for treatment with metformin;
• in combination with metformin and a sulphonylurea or a PPAR-gamma agonist in patients not sufficiently controlled with the two drugs;
• in combination with insulin, with or without metformin, in patients insufficiently controlled with a fixed insulin dose.
The medicine can only be obtained with a prescription.
How is Ristaben used?
The recommended dose of Ristaben is 100 mg once a day, to be taken with or without food. If Ristaben is taken in combination with a sulphonylurea or insulin, it may be necessary to reduce the dose of the latter to reduce the risk of hypoglycaemia (low blood sugar level).
How does Ristaben 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 the available insulin effectively. The active substance in Ristaben, sitagliptin, is a dipeptidyl-peptidase-4 inhibitor (DPP 4) and works by blocking the breakdown of incretins in the body, hormones released after meals that stimulate the production of insulin in the pancreas. By increasing incretins in the blood, sitagliptin stimulates the pancreas to produce more insulin where the blood sugar is too high. Sitagliptin is not effective if blood sugar is low. Sitagliptin also reduces the amount of glucose produced by the liver by increasing insulin and reducing the levels of glucagon, a hormone. Together these processes reduce blood sugar and help control type 2 diabetes.
How has Ristaben been studied?
Ristaben has been the subject of nine studies involving nearly 6, 000 patients with type 2 diabetes and with insufficiently controlled blood glucose:
• Four of these studies compared Ristaben with a placebo (a dummy treatment). Ristaben or placebo were used alone in two studies involving a total of 1 262 patients, in addition to metformin in a study of 701 patients and in addition to pioglitazone (PPAR-gamma agonist) in a study of 353 patients;
• two studies compared Ristaben with other anti-diabetic drugs. One study compared Ristaben and glipizide (a sulphonylurea) as additional treatments for metformin in 1 172 patients. The other study compared Ristaben and metformin, used alone, in 1 058 patients;
• three other studies compared Ristaben and a placebo used in addition to other antidiabetics: glimepiride (a sulphonylurea), with or without metformin, on 441 patients; the metformin / rosiglitazone combination (PPAR-gamma agonist) in 278 patients; a fixed dose of insulin, with or without metformin, in 641 patients.
In all the studies the main measure of effectiveness was the effect of the medicines on the blood levels of a particular substance, glycosylated hemoglobin (HbA1c), which is indicative of the effectiveness of glycemic control.
What benefit has Ristaben shown during the studies?
Ristaben was more effective than placebo when taken alone or in combination with other diabetes medications. From about 8.0% at the start of the study, in patients taking Ristaben alone, HbA1c levels fell 0.48% after 18 weeks and 0.61% after 24 weeks. By contrast, these levels increased by 0.12% and 0.18% respectively in patients treated with placebo.
The addition of Ristaben to metformin reduced HbA1c levels by 0.67% after 24 weeks, compared with a reduction of 0.02% in patients who had added placebo. The addition of Ristaben to pioglitazone reduced HbA1c levels by 0.85% after 24 weeks, compared with a reduction of 0.15% in patients who had added placebo.
In studies comparing Ristaben and other drugs, the effect of adding Ristaben to metformin was similar to that obtained by adding glipizide. Taken alone, Ristaben and metformin induced similar reductions in HbA1c levels, although Ristaben seemed slightly less effective than metformin.
In the other studies the addition of Ristaben to glimepiride (with or without metformin) led to a reduction in HbA1c levels of 0.45% after 24 weeks, compared to the 0.28% increase observed in patients where it had been added the placebo. HbA1c levels were reduced by 1.03% after 18 weeks in patients in whom Ristaben was added to metformin and rosiglitazone compared to the 0.31% reduction recorded in patients with placebo addition. Finally, there was a 0.59% reduction in patients in whom Ristaben was added to insulin (with or without metformin) compared to the 0.03% reduction obtained in patients with placebo addition.
What are the risks associated with Ristaben?
The most common side effects associated with Ristaben (generally seen in more than 5% of patients) include infections of the upper respiratory tract (cooling) and nasopharyngitis (inflammation of the nose and throat). For the full list of all side effects reported with Ristaben, see the Package Leaflet.
Ristaben should not be used in patients who may be hypersensitive (allergic) to sitagliptin or any of the other ingredients.
Why has Ristaben been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that Ristaben's benefits are greater than its risks and recommended that it be given marketing authorization.
More information on Ristaben
On 15 March 2010, the European Commission issued a marketing authorization for Ristaben, valid throughout the European Union, to Merck Sharp & Dohme Ltd. The marketing authorization is valid for five years, after which it can be renewed.
The full EPAR for Ristaben can be found here. For more information on treatment with Ristaben, read the package leaflet (also part of the EPAR).
Last update of this summary: 01-2010.
