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Wednesday, October 18, 2006

Metformin: A Beginner's Guide

For centuries people have used French Lilac (Galega officinalis) to treat the symptoms of diabetes mellitus. But it was only in the last century that the active ingredient was isolated and identified. This compound, a single guanidine ring, while itself being too toxic to be used in the long term management of diabetes, led to the development of one of the safest and most widely used of all the antidiabetic medications: metformin.

Metformin belongs to a group of drugs called the biguanides, which consist of two linked guanidine rings. Although it has been used to treat diabetes for at least thirty years, it is only now that we are beginning to get an idea of how it works, even though the exact mechanisms of action remain more or less a mystery.

What we do know, however, is that metformin has a number of different effects on glucose metabolism. These effects lead to improved insulin sensitivity in tissues such as muscle and liver as well as decreased gluconeogenesis ( the synthesis of glucose from non-carbohydrate sources ) by the liver. The net result of these and certain other actions is a decrease in glucose levels. However, because metformin is a euglycaemic agent, blood glucose levels do not fall below normal. Hypoglycaemic episodes do therefore not usually occur.

Metformin also has beneficial effects on lipid metabolism, and tends to result in a lowering of circulating fatty acids and VLDL, both of which are known to be involved in causing cardiovascular disease.

Conclusion? Metformin is an extremely effective treatment for type 2 diabetes, because it acts at the source of the problem: it combats insulin resistance. It has been shown to delay and even prevent the onset of type 2 diabetes in people with impaired glucose tolerance and insulin resistance. And it decreases the risk of diabetes-related death, as well as heart attacks and strokes, in people who already have diabetes. Metformin saves lives.

In addition to this, metformin is used with great effect in the treatment of polycystic ovarian syndrome, both improving the symptoms of the condition, and increasing by up to eight-fold the probability of ovulation (and so substantially increasing fertility). It also appears to be safe to use during pregnancy, and significantly decreases the risk of women with PCOS developing gestational diabetes.

Metformin clearly has great benefits for those with insulin resistance and related conditions (such as PCOS, type 2 diabetes and metabolic syndrome). Unfortunately these benefits may come at a price – metformin causes some fairly uncomfortable side effects in some people. These include nausea, loss of appetite, a metallic taste, and diarrhoea, which may or may not be severe. These side effects tend to be present at the start of treatment and with higher doses of the drug. It is most likely that some of the side effects are caused by residual amounts of the drug (in other words, the quantity of metformin that is not absorbed by the gastrointestinal tract) which remains in the bowel and causes irritation and subsequent diarrhoea.

Most of these adverse effects may therefore be controlled by starting treatment on very low doses and slowly increasing the amount of drug taken to achieve the desired results. The absorption of metformin is also increased by taking the medication with food, which leaves less of the drug remaining in the gastrointestinal tract to cause irritation and diarrhoea. Nausea may be improved by taking the medication in divided doses e.g. 500mg every eight hours instead of all at once. The newer sustained release formulations may also help with this problem. It is important to be aware that, in general, all the side effects associated with metformin improve with time.

Another more important, but much rarer risk, is that of lactic acidosis. This seldom occurs unless there are underlying problems such as kidney or liver disease, or heart failure, or if the daily dose of metformin used exceeds the current recommended maximum of 2550mg for adults (or 2000mg extended release formulations) and 2000mg for children. Symptoms of lactic acidosis include weakness, muscle pain, difficulty breathing, stomach pain, dizziness and a slow heartbeat. This is a very dangerous condition, and needs to be treated immediately. Fortunately it is so rare that it is very seldom seen. Having said all this, metformin still has the ability to change peoples’ lives in ways seldom mentioned in medical texts. It relieves the chronic tiredness that people with insulin resistance experience, and decreases cravings for carbohydrates. It also makes weight loss that much easier for people who have always struggled to lose a few pounds, and keep them off.

In conclusion, it may be said that metformin is a relatively safe and effective drug, which has the ability to increase both the quantity and quality of life in those of us unlucky enough to have insulin resistance

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