Komboglyze - Saxagliptin / metformin

What is Komboglyze - Saxagliptin / metformin?

Komboglyze is a medicine that contains active substances such as saxagliptin and metformin and is available as tablets (2.5 mg / 850 mg or 2.5 mg / 1 000 mg).

What is Komboglyze - Saxagliptin / metformin used for?

Komboglyze is indicated in addition to diet and exercise to improve glycemic control in patients with type 2 diabetes for which the glycemic rate is not adequately controlled with metformin alone (another antidiabetic) or in those patients already being treated with the combination saxagliptin and metformin in separate tablets.

The medicine can only be obtained with a prescription.

How is Komboglyze - Saxagliptin / metformin used?

Komboglyze is taken as one tablet twice a day with meals. Patients not adequately controlled on metformin alone (starting alone) who start treatment with Komboglyze should still receive the usual dose of metformin. Patients adequately controlled with the combination saxagliptin and metformin in separate tablets switching to a Komboglyze regimen should take the tablet containing the same doses of the components.

How does Komboglyze - Saxagliptin / metformin 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 ingredients of Komboglyze, saxagliptin and metformin, each act differently to help reduce the glycemic rate and control type 2 diabetes.

Saxagliptin is an inhibitor of dipeptidyl peptidase 4 (DPP4). It works by inhibiting the degradation of "incretin" hormones in the body. These hormones are released after food and stimulate the pancreas to produce insulin. By increasing the level of incretin in the blood, saxagliptin stimulates the pancreas to produce more insulin when the blood sugar level is high. Saxagliptin is ineffective when blood glucose concentration is low. Saxagliptin also reduces the amount of glucose produced by the liver by increasing insulin levels and decreasing the levels of the glucagon hormone. In the European Union the use of Saxagliptin was authorized in 2009 with the drug Onglyza.

The active ingredient metformin acts mainly by blocking the production of glucose and reducing its absorption in the intestine. Metformin has been available in the EU since the 1950s.

Due to the action of the two active ingredients, blood glucose levels are reduced allowing the control of type 2 diabetes.

How has Rasitrio been studied?

Before being studied in humans, the effects of Komboglyze were analyzed in experimental models.

The manufacturer presented the results of a new main study conducted on patients with type 2 diabetes, along with the results of five other studies that had already been evaluated for Onglyza's authorization.

The new study examined the effects of saxagliptin 2.5 mg taken twice a day, compared with those of the placebo added to metformin in 160 patients whose blood glucose values were not adequately controlled with metformin alone. The effects were analyzed after 12 weeks of treatment. The other five studies analyzed the effects of saxagliptin (in different dosages) used as monotherapy or in combination with metformin in over 4, 000 patients with type 2 diabetes, compared to placebo or a comparator (sulfonylurea or sitagliptin). In all the studies, the main efficacy index was the change in the levels of a substance present in the blood called glycosylated hemoglobin (HbA1c), which provides an indication of the level of efficacy of blood glucose control.

The manufacturer also presented the results of a study conducted on 32 healthy subjects in which blood saxagliptin levels were observed when taking a dose of 2.5 mg twice a day compared to a dose of 5 mg once a day.

What benefit has Rasitrio shown during the studies?

In the main study, patients receiving saxagliptin 2.5 mg taken twice daily in combination with metformin showed a 0.6% reduction in HbA1c levels, compared with a 0.2% reduction in patients treated with placebo in combination with metformin. Furthermore, it emerged from the other five studies that the addition of saxagliptin to metformin was effective in reducing HbA1c levels.

The study in healthy subjects showed that, over a 24-hour period, taking 2.5 mg of saxagliptin twice a day produces the same levels of active substance in the blood as with a once-daily intake of 5 mg per day.

What is the risk associated with Rasitrio?

The most common side effects seen with saxagliptin (seen in between 1 and 10 patients in 100) are upper respiratory tract infections (colds), urinary tract infections (urinary tract infection such as the bladder), gastroenteritis (diarrhea and vomiting), sinusitis (inflammation of the paranasal sinuses), nasopharyngitis (inflammation of the nose and throat), headache, vomiting, nausea (feeling sick) and rash. The most common side effects seen with metformin (seen in more than 1 patient in 10) are gastrointestinal symptoms (affecting the stomach and intestines). For the full list of all side effects reported with saxagliptin and metformin, see the Package Leaflet.

Komboglyze should not be used in patients who are hypersensitive (allergic) to saxagliptin and metformin or any of the other substances, or who have experienced a severe allergic reaction to one of the DPP4 inhibitors. It is contraindicated in patients with diabetic ketoacidosis or diabetic pre-coma (a dangerous condition that can occur due to diabetes), moderate or severe renal failure or acute (sudden) states that can alter renal function, acute or chronic diseases that can cause tissue hypoxia (which occurs when the tissue lacks adequate oxygen supply) such as heart or respiratory failure, liver failure, acute alcohol intoxication or alcoholism. It should not be administered during breastfeeding. For the full list of limitations, see the package leaflet.

Why has Komboglyze - Saxagliptin / metformin been approved?

The CHMP came to the conclusion that Komboglyze helps reduce blood glucose levels in patients whose blood glucose values are not adequately controlled with metformin alone, while the combination of saxagliptin and metformin administered in a single tablet can help patients who are already they take both substances to follow the treatment correctly. The CHMP also noted that this combination does not cause unexpected side effects; therefore, decided that Komboglyze's benefits are greater than its risks and recommended that it be given marketing authorization.