Biguanides
The biguanides were introduced in 1957. Both phenformin and metformin have been widely used here, although in recent times, the use of phenformin has decreased significantly and most people now use metformin when a biguanide is to be used.

Metformin is a chemical cousin to the French lilac plant, which was noted to lower blood sugars in the early 1900s. However, French lilac turned out to be too toxic for use in humans.

Initially it was felt that metformin acted by reducing the appetite and thus decreasing food intake. It also decreases the absorption of food from the small intestines. Now we know that main site of action of metformin is the liver. Metformin lowers blood glucose levels by increasing the sensitivity of the liver cells ( and some muscle cells, too) to insulin. This leads to an increased uptake of the raised blood glucose levels in the immediate post food period and a decrease in the production of "new" glucose by the liver at a later time.

Metformin is usually taken two to three times each day with a meal. Your doctor will tell you which meals to take it with. Once daily doses of metformin are available in the market, but are still not widely accepted by most doctors.

Metformin has several advantages:

a) Lower blood sugars, especially after eating, with no risk of hypoglycemia

b) Improved lipid levels with total cholesterol and LDL levels dropping about 10 percent, triglycerides by as much as 50 percent, while protective HDL levels rise about 10 percent

c) Mild reductions in weight and blood pressure

Side Effects

• Metformin can make you sick if you drink more than about two to four alcoholic drinks a week. If you drink more than that, you need to tell your doctor. You probably shouldn't take this medication.
• If you already have a kidney problem, metformin may build up in your body. Make sure that your doctor knows your kidneys work well before you are placed on this medication.
• If you are vomiting, have diarrhea, and can't drink enough fluids, you may need to stop taking this medication for a few days.
• Occasionally, people on this medication can become weak, tired or dizzy and have trouble breathing. If you ever have any of these symptoms, call your doctor or get medical attention immediately.
• You may have nausea, diarrhea and other stomach problems when you first start taking metformin. These usually go away, but you should check with your doctor if you are experiencing these symptoms.
• You may notice the taste of metal in your mouth.
• If you are having surgery, tell the surgeon you are taking metformin. You should be told to stop taking this medication on the day of surgery. Then you shouldn't take it again until you are eating and your kidneys are working normally.
• If you have a medical test using dye, tell the doctor you are taking metformin. You may be told to stop taking metformin the day of the test and not to take the medication again for 48 hours.

Drug Interactions
There are drugs which interact with metformin. It is absolutely essential that you tell your doctor all the medications which you are taking.

Alpha-glucosidase inhibitors
Acarbose is an alpha-glucosidase inhibitor that slows down the breakdown of disaccharides and polysaccharides and other complex carbohydrates into monosaccharides. The enzymatic generation and subsequent absorption of glucose is delayed and the postprandial blood glucose values, which are characteristically high in patients with type II diabetes, are reduced with acarbose. AGIs do not prevent the absorption of carbohydrates and complex sugars, but they do delay their absorption. Delaying the absorption of carbohydrates is a unique mechanism among oral diabetic medications for lowering HgbA1c levels. The effectiveness of this mechanism is one of the physiologic characteristics of type 2 diabetes. Patients with type 2 diabetes demonstrate a delayed or sluggish insulin response from the pancreas to a glucose (a meal) load. By delaying the absorption of glucose, the insulin response is more matched to the serum glucose, resulting in less postprandial hyperglycemia and a lowering of the HbA1c. The AGIs also demonstrate a lowering of total insulin output of the pancreas, increased insulin sensitivity, a variable but mild decrease in triglycerides, with no effect on patient weight.

Acarbose is taken three times daily, at meals, although your doctor might ask you to take the medication less often at first One disadvantage with the use of acarbose is that it is to be taken along with the first bite of a meal. Moreover, it has to be taken three times daily with meals. These factors often lead to non compliance and a decrease in the efficacy of the drug.

Side Effects
The way in which these drugs work is also the major source of their side effects. Although these drugs are very safe, their side effects can be annoying. If digestion is greatly inhibited, this may cause abdominal bloating, gas and diarrhea. The alpha glucosidase inhibitors should always be started on a minimal dose, often half of the smallest tablet, and then gradually increased over time. This greatly minimizes gastric side effects; side effects also tend to decrease over time.

Since the drugs cause intestinal discomfort, they should not be taken by anyone who already has medical problems with digestion or absorption.