Metformin – medication for Diabetes type 2

Hello friends!

The drug metformin is the subject of our discussion today.

In certain cultures, diabetes mellitus, a condition that causes hyperglycemia or high blood sugar, has been called the rich man’s disease. That’s a reference to type 2 diabetes which is associated with an over-abundance of food intake and resulting obesity.

In people with no diabetes, as the glucose in the blood increases, the beta cells of the pancreas release a hormone called insulin, that sets off biochemical processes resulting in the use of sugar for energy or storage of sugar in the body. In diabetics, this biochemistry is compromised.

Most people with diabetes have one of two kinds, type 1 and type 2. There are several other forms of diabetes too, but that can be the subject of another article. Type 1 diabetes is due to deficient production and/or release of insulin by insulin-producing beta cells, possibly due to genetic factors. Some scientists have suggested that some type 1 diabetes could be due to an auto-immune mechanism, where the body destroys its own beta cells in response to a viral infection. Insulin injections are pretty much the only way the blood sugar can be controlled in type 1 diabetes.

Type 2 diabetes or adult onset diabetes mellitus is the focus of our interest here. There are genetic and environmental factors at work here. The beta cells make insulin, but the body is not able to use it properly. In recent times, the incidence of diabetes has risen to almost pandemic proportions. Worldwide, 6% of the adult population is afflicted. In the USA, 7-8% of the population are diabetics. Increase in diet and decrease in physical activity are to blame. There is a condition called metabolic syndrome – abdominal fat, high blood pressure, high triglycerides, low high-density lipoprotein or HDL, and insulin resistance – these are all risk factors.

Let’s step back for a moment. So, there’s an increase in blood glucose. What’s the big deal? Here’s what happens. We eat food. The food is absorbed. Routine biochemical pathways create glucose from the carbohydrates we eat. Glucose levels rise in the blood. Insulin that is synthesized by the beta cells of the pancreas is released, resulting in the uptake of glucose by body cells – as a result, the blood glucose levels fall to normal levels. In diabetes, blood glucose levels remain high.

In extreme cases, when blood glucose levels are too high, the blood osmotically draws out water from cells. The kidney gets rid of the extra water with dissolved glucose in the urine. This can lead to dehydration, electrolyte imbalance and eventually diabetic coma.

When blood glucose levels remain chronically high, the cells lining blood vessels absorb high levels of glucose. These link to proteins and thicken the blood vessel membrane. This makes the blood vessel weak.

Microvascular (micro = small, vascular = pertaining to blood vessels) damage is when small blood vessels are weakened – this results in a lot of diabetic complications. When the small blood vessels of the retina are affected, the resulting diabetic retinopathy can even lead to blindness. Diabetic neuropathy is when the small blood vessels in the feet and hands are affected – it creates a tingling sensation, numbness and can lead to skin ulcers, even cell death and gangrene. Amputation may be necessary. Diabetic nephropathy is damage to the small blood vessels of the kidneys, leading to chronic kidney failure, necessitating dialysis. Diabetic cardiomyopathy is damage to small blood vessels of the heart.

Macrovascular damage affects the arteries. This can lead to a heart attack, stroke, peripheral vascular disease with poor circulation in the extremities, and death of muscle tissue. These problems can be accelerated by high cholesterol and atherosclerosis.

See what problems are created by high blood glucose?

What happens once type 2 diabetes mellitus is diagnosed? The American Diabetes Association recommends diet, exercise and first-line treatment with metformin. The brand names of metformin are Glucophage and Glumetza, among others. It belongs to the biguanide class of antidiabetic medicine. Historically, a plant called French lilac (scientific name Galega officinalis) has been used since the Middle Ages to treat diabetes. A chemical called guanidine is the active ingredient. Metformin is a chemical derivative of guanidine.

What does metformin do? It uses insulin better. What is the mechanism of action? It boosts the activity of a liver enzyme called adenosine monophosphate-activated protein kinase (AMPK). This results in an increased expression of a genetic factor called SHP (small heterodimer partner) which inhibits the genetic expression of a couple of liver enzymes. This results in decreased glucose synthesis by the liver. Metformin also induces better binding of insulin to insulin receptors – due to which there is better utilization of glucose by peripheral cells. It also decreases the absorption of glucose by the gastro-intestinal tract. And, it decreases the breakdown of fat for energy.

Some other beneficial effects of metformin are reduction of LDL cholesterol and triglycerides, and weight loss.

Metformin has very few side-effects. Gastrointestinal upset can occur – nausea, diarrhea and flatulence. This can be reduced by administering extended release metformin tablets, or by starting with a low dose and slowly increasing the dose, and by taking it with food. Lactic acidosis is another possible side effect, mostly in patients with less than perfect liver and kidney function. In this situation, there is too much lactic acid build-up – this happens when glucose is used with not enough oxygen. It results in irregular breathing, and gastro-intestinal upset.

So far, modern medicine has no cure for diabetes. The only option available is treatment, so that blood glucose levels are maintained at normal levels. If this is done by means of right eating and exercise as mentioned above, and the prescribed medication, one can live long, productive lives. If the glucose levels are allowed to rise, or even fluctuate, we saw how it can affect all essential systems of our body. If you have been diagnosed with diabetes, please do make sure you check your blood glucose levels regularly, as directed by your doctor.

And, as we have discussed before …. think good thoughts, and laugh a lot ……. Wish you good health!

Let’s connect again …… same time next week ……..

Dr. Ajit Damodaran

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