What is pioglitazone?
Pioglitazone is a drug from the group of insulin sensitizers, which is used for the treatment of diabetes mellitus type 2 in the form of tablets. The active principle is a sensitization (increased sensitivity) of the tissue to insulin, its effect is reduced in the insulin resistance typical of this form of diabetes. The endogenous or supplied by insulin injections is therefore again able to lower elevated blood sugar levels effectively.
Application
In obese patients, pioglitazone is used in combination with metformin. The medicament is administered orally. In patients who can not tolerate metformin or for whom metformin is contraindicated, pioglitazone can be used in monotherapy (pioglitazone only) or combination with a sulphonylurea. It is also possible to pioglitazone in triple therapy use (with metformin and sulfonylureas), the combination with insulin is possible. Taking the tablets with or without food can take place. The effect of pioglitazone occurs immediately, but is fully formed only after about 4 weeks. An exception is the combination with insulin, since in this case the effect of insulin is directly amplified. There should be close monitoring of blood sugar levels to avoid hypoglycemia (hypoglycemia).
Pioglitazone can be prescribed only in exceptional cases, at the expense of the statutory health insurance following a decision by the Federal Joint Committee since April 2011.
Pioglitazone mechanism of action
In the body cells pioglitazone activated in the nucleus of the PPAR receptor (peroxisome-proliferator-activated receptor-gamma). This receptor is involved in the regulation of various mechanisms in the carbohydrate and lipid metabolism. Activation of this receptor increases the sensitivity of the cells of the liver, muscle and fat insulin. Blocks fat and glucose are thus increasingly absorbed and metabolized in the cells. In the liver, reduces the formation of glucose.
The blood sugar level decreases both fasting and after meals. Also increased insulin levels after meals are lowered. The increased effect of existing insulin the body requires only relatively small amounts of insulin. An existing insulin resistance increases by pioglitazone from hence.
The active ingredient pioglitazone reduced by the same mechanism as all glitazones, insulin insensitivity (insulin resistance) of adipose tissue, the muscles and the liver and thus lowering blood sugar levels. In addition, pioglitazone can reduce the sugar production in the liver and improve glucose utilization in the body, for example in the muscles. Thus, the glucose metabolism is also optimized.
In addition to improving the efficiency of the body's own insulin, pioglitazone also increases the effect of added insulin. The onset of action of pioglitazone that can wait about two to three weeks to be in individual therapy, occurs in combination with insulin, a significantly faster. Taking pioglitazone, the patient must reduce partially his insulin dose by up to 30 percent to prevent hypoglycaemia. Sometimes it is even possible to completely discontinue the insulin. However, switching to the combination may only be done under supervision of a physician experienced in the treatment of diabetes physician and with very frequent follow-up visits.
Contraindications
Patients with hepatic impairment should not take pioglitazone. In addition, patients with heart failure, ie heart failure, pioglitazone should not be given. This also applies if the heart failure in the past was present.
There is no experience with the use of pioglitazone in pregnant women and nursing mothers. The use of the substance in these patients must therefore be omitted. For the use of pioglitazone in patients with severe renal impairment, in dialysis patients and in children and adolescents below 18 years there has been no sufficient experience. Pioglitazone should therefore not be used in these patient populations.
Pioglitazone side effects
The increased uptake of fatty components from the blood has the undesirable consequence that increased body fat and adipose tissue is formed and the result is obesity. The body weight may therefore increase during treatment with pioglitazone and makes regular weight checks required. In addition, pioglitazone increase the amount of water in the body and also increased water retention in the tissue occur.
In randomized controlled trials for long-term use has also been reported from a vermehrtem fracture risk. Accordingly valley the drug, especially in women, bone density in the lumbar spine and the hip, which is why the authors advise against treatment with glitazones in women at increased risk of fracture.
In September 2010, the US Food and Drug Administration prompted the review of pioglitazone on the risk of bladder cancer trigger. Previously, in two clinical studies an increased morbidity (incidence) was observed for bladder cancer among Pioglitazongabe. In March 2011, followed by a initiated the Committee for Human Medicinal Products of the European Medicines Agency review. In France, the competent authority Afssaps arranged in June 2011 after the completion of a cohort study, which had also found a trend toward a higher risk of bladder cancer, the withdrawal of medication for pioglitazonhaltige. The German Federal Institute for Drugs and Medical Devices advised in the same month from getting patients to readjust to a pioglitazonhaltiges drug, the manufacturer issued a corresponding Rote-Hand-Brief. The European Medicines Agency introduced at a slightly increased risk for the development of bladder cancer continues a positive benefit-risk ratio fixed, justifying a carefully controlled therapy, and advises only from in susceptible patients, by treatment with pioglitazone. In July 2011, the manufacturer Takeda published another Red Hand Letter.