What is metformin?
Metformin is a drug from the biguanide class, the case of non-insulin-dependent diabetes (type 2 diabetes mellitus) and in particular in light-weight (pre-obese) and morbid obesity (obesity) is used. It is one of antidiabetic used the longest and certainly the most common. Studies show that it decreases as the only occurrence of cardiovascular events in type 2 diabetes.
Operating principle
The molecular mode of action of biguanides is still not fully understood. Clinical studies show that Metformin inhibits glucose formation in the liver. In addition to the intake of sugar (glucose) in the diet provides this pathway, is obtained with the glucose from the conversion of amino acids and other metabolites, is an important determinant of blood sugar levels. Again and again also noted that metformin addition the absorption of glucose inhibit the intestine and should result in faster uptake in the muscle cells, but these two effects could not be detected reliably so far. Nevertheless bodybuilder metformin should abuse to fat loss. Due to the favorable effect on body weight in adults was trying metformin in obese children to use - but without the desired effect. Metformin has been used successfully for years in the treatment of polycystic ovary syndrome, where it appears to the abnormally increased production of the male sex hormone testosterone blocked. It opened on polycystic ovary syndrome affected women a way to still be pregnant. Officially metformin is however not so authorized, thus corresponds to a so-called off-label use, what the patients should be informed. Also the drug for this reason is not to prescribe in this indication by the statutory health insurance.
Contraindications
For an absolute insulin deficiency such as type I diabetes, diabetic ketoacidosis or diabetic coma the metformin is completely unsuitable (contraindicated).
Metformin should not be used in renal failure, liver failure, alcoholism or such circumstances as well, which can promote acidification by lactic acid. This includes heart failure or as a juice fast. Myocardial infarction, shock or severe infections prohibit its use.
In pregnancy there is in Germany a strict indication, since it is not approved for this indication. Evidence of a teratogenic effect have so far (as of 2010) in all studies can not be found. Metformin crosses the placenta and is excreted in breast milk. It should be used during pregnancy and in nursing mothers only in justified cases, in the form of a so-called therapeutic trial (eg if the required insulin doses are very high).
Prior to surgery, anesthesia, studies with intravascular administration (via the blood) of contrast agents or intensive care metformin at least 24 hours to 48 hours before the event to be discontinued due to the risk of acidosis (acidosis) in the blood (lactic acidosis).
What are the side effects of metformin?
Taking into account the contraindications occur as a side effect often and usually only at baseline gastrointestinal complaints such as diarrhea, nausea and vomiting. With the supervising physician is essential to consult to keep. By slow, creeping dose over 2-3 weeks, these side effects can often be circumvented. It recommends against the background that this ingredient of the otherwise low side effect drug proven by many studies (see below) has a broad spectrum of activity, in any case, a patient try several products before discontinuation of therapy is being considered.
The Drug Commission of the German Medical Association (AKdÄ) reported in March 2013 on the "increase of spontaneous reports of metformin-associated lactic acidosis" ("From the ADR database").
An uncommon cause of these side effects can be a lactose intolerance, as a preparation containing lactose as an excipient. In this case prescribe a lactose-free preparation of the doctor. According to a recent survey contains 31 single-ingredient products available in the German-speaking area of the indication of lactose in the list of additives (trade name Met).
In infections with massive vomiting and persistent diarrhea, severe metformin should be discontinued due to the risk of acidification of the organism. Especially in patients with renal failure and in the context of life-threatening lactic acidosis can occur anesthesia.
A hypo (hypoglycaemia) does not occur under the sole therapy with metformin, but may occur after excessive alcohol consumption, as alcohol itself lowers blood sugar levels.
After a clinical trial is in long-term use of metformin increased risk for vitamin B12 deficiency.
Alcohol intake
The risk of lactic acidosis is increased by co-administration of metformin and a larger amount of alcohol. In alcohol-dependent patients metformin is contraindicated. At the risk of lactic acidosis metformin, however, is much lower than with phenformin, which is no longer commercially due to this risk in Germany. Therefore applies to patients who are taking metformin, an occasional moderate alcohol intake with a carbohydrate-containing meal connected as harmless. This means that women have a glass of wine, sparkling wine can consume twice (women up to 10 g alcohol / day, men to 20 g alcohol / day) with a meal (about 100 ml) or beer (about 250 ml) and men accordingly. Carbohydrate-rich alcoholic beverages should be avoided.
Dosage and opportunities
Metformin is available in dosage strengths of 500 mg, 850 mg and 1000 mg are available in order to make an individual blood sugar control can. The tablets are administered orally or after meals.
Metformin Although the time of ingestion of the effect does not matter, but a dose (diarrhea) compatibility is immediately after meals, in the interest of better gastrointestinal recommended.
After an initial phase of approximately 14 days, in which one goes low or medium strong doses, dose adjustments based on blood glucose levels is usually necessary.
Metformin should be used according to the guidelines of the German Diabetes Society as first-line therapy with nutritional counseling as a single agent. If so do not set adequate blood glucose lowering, it can be combined with other oral antidiabetic agents, such as sulfonylureas or insulin sensitizers or the dipeptidyl peptidase-4 inhibitors as well as with insulin.
To increase patient compliance (compliance) and to reduce the number of tablets to be fixed combinations of an insulin sensitizer such as pioglitazone have been put on the market with metformin and DPP4 inhibitors such as vildagliptin with metformin.
Metformin side effects
Several studies suggest that metformin may reduce the risk of cancer in type 2 diabetic patients. In a 2009 published in the journal Diabetes Care study showed for the examined subjects, a significant difference between the groups in terms of new cases of cancers: From the metformin engaging patients affected 7.3 percent of cancer. In the diabetics without metformin cancer was found in 11.6 per cent. The time to onset of cancer was 2.6 years in the metformin group on average 3.5 years and in the comparison group. It showed a lower cancer-related mortality rate of metformin engaging study participants. Taking into account possible confounders such as sex, age, BMI, HbA1c, poverty (measured by the so-called Carstairs score), smoking and taking other drugs, was under metformin a reduced risk of cancer by 37 percent. Other studies, for example, associated with colorectal, prostate or breast cancer show the same direction results.
In a 2011 meta-analysis published on 5 studies with a total of 108,161 type 2 diabetes treatment with metformin resulted in a significantly reduced risk for the development of malignant tumors of the rectum. However, molecular biological or -genetische explanations not found themselves, therefore, further studies remain necessary.