Actos - pioglitazone

What is Actos?

Actos is a medicine that contains the active substance pioglitazone. White round tablets contain 15, 30 or 45 mg of pioglitazone.

What is Actos used for?

Actos is used to treat type 2 diabetes (also known as non-insulin-dependent diabetes).

• It can be used alone (monotherapy) in patients (especially if overweight) who cannot take metformin (an antidiabetic medicine).

• It can be used together with another antidiabetic medicine (dual therapy). It can be added to metformin in patients (especially if overweight) who are not adequately controlled with metformin alone at the maximum tolerated dose; or it can be added to a sulphonylurea (another antidiabetic drug) when metformin is contraindicated and patients are not adequately controlled with the sulphonylurea alone at the maximum tolerated dose.

• It can be used together with two other antidiabetic medicines, metformin and a sulphonylurea, as triple therapy in patients (especially if overweight), who are not sufficiently controlled with these two medicines.

• It can be used together with insulin in patients who are not sufficiently controlled with insulin alone and cannot take metformin.

How is Actos used?

Actos should be taken once a day, out of meals or with meals. The dose is adjusted to get the best effect. The recommended starting dose is 15 mg or 30 mg once a day. It may be necessary to increase the dose after one or two weeks up to 45 mg once a day. In combination with metformin the current metformin dose can be continued when starting treatment with Actos. In combination with a sulphonylurea or with insulin, the current dose of sulphonylurea or insulin can be continued when starting treatment with Actos, provided the patient does not suffer from hypoglycemia (low blood glucose concentration), in which in case the dose of sulphonylurea or insulin has to be decreased.

How does Actos work?

Type 2 diabetes mellitus is a disease in which the pancreas does not produce enough insulin to control the level of glucose in the blood. The active ingredient in Actos, pioglitazone, makes cells more sensitive to insulin, so the body uses better the insulin it produces, the rate of glucose in the blood is reduced and this serves to control type 2 diabetes.

What studies have been carried out on Actos?

Actos has been studied in clinical pharmacology and clinical trial studies. In total, around 7, 000 patients received Actos. Actos was compared with placebo (a dummy treatment) or other antidiabetic medicines (metformin, gliclazide) during these studies. In some studies Actos has also been examined in combination with other antidiabetic drugs (sulfonylureas, insulin, metformin). In triple therapy, the efficacy of Actos was studied in over 1, 400 patients who received a combination of metformin and a sulphonylurea, to which Actos or placebo was added for a period of up to 3.5 years.

These studies measured the concentration in the blood of a substance (glycosylated hemoglobin, HbA1c) that gives an indication of the effectiveness of blood glucose control.

What benefit has Actos shown during the studies?

Actos induced a decrease in HbA1c, showing that blood glucose levels had decreased with dosages of 15 mg, 30 mg and 45 mg. Dosages below 15 mg were not effective and dosages above 45 mg (once a day) did not show any additional benefit. Taken as monotherapy, Actos was as effective as metformin and gliclazide. Taken in combination, Actos has been shown to improve type 2 diabetes control when added to ongoing therapy. At the end of the triple therapy study, the effect of adding Actos to the current treatment with metformin and a sulfonylurea was a 0.94% reduction in HbA1c levels, while the addition of the placebo led to a reduction of 0.35%. In a small study of the combination of Actos and insulin in 289 patients, patients for whom Actos was added to insulin achieved a 0.69% reduction in HbA1c levels after 6 months, compared to 0.14% in the case of placebo.

What is the risk associated with Actos?

The most common side effects seen with Actos were visual disturbances, upper respiratory tract infections (colds), weight gain and hypoesthesia (decreased sensitivity to stimuli). For the full list of all the side effects reported with Actos, see the Package Leaflet.

Actos must not be used in patients who are hypersensitive (allergic) to pioglitazone or to any of the excipients or in patients with liver problems, heart failure or diabetic ketoacidosis (high concentration of ketones [acids] in the blood).

Why has Actos been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Actos' benefits are greater than its risks for the treatment of type 2 diabetes. The committee recommended that Actos be given marketing authorization. The committee decided that, on its own (ie when used alone), Actos should be considered an alternative to the standard treatment (metformin) in patients for whom metformin is contraindicated.