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What if Diet and Exercise Don't Control my Glucose Adequately?

Oral Hypoglycemic Agents (Pills)

Most people with Type 2 diabetes will not require insulin to control their glucoses. However, if exercise and proper eating are not adequate to control blood sugars, pills are usually required.

These are not "insulin pills". At the present time, insulin cannot be given in pill form — like any other protein, it would be digested before the body could absorb it. The pills currently available in Canada include Sulfonylureas, Metformin, Acarbose, Gluconorm and Thiazolidinediones.

All pills have potential side effects, so check with your doctor if you experience any abnormal symptoms when taking glucose-lowering drugs. Some of the side effects are self-limiting (they go away with time).


This group of agents includes Glyburide (available under many names such as Diabeta, Euglucon, and others), Gliclazide (available as Diamicron), Chlorpropamide, Diabenese, and Tolbutamide. All sulfonylureas act in the same way: they attach to the insulin-producing cells of the pancreas (the beta cells), and tell them to put out more insulin than they would normally. Insulin levels in the blood go up, bringing down the glucose. These pills can also make blood glucose go too low (see section on hypoglycemia).

These drugs are generally very well tolerated, and side effects are rare. Typical side effects include hypoglycemia and weight gain. More rarely, sulfonylureas can cause diarrhea, gas and skin reactions (including sun sensitivity). These pills should not be taken by pregnant women, anyone with with severe allergies to sulfa drugs, and those with severe kidney or liver disease.


Metformin (also referred to as Glucophage) is a member of a class of drugs called biguanides. Its major action is to lessen the amount of glucose produced by the liver. Recall that in people with diabetes, the liver overproduces glucose, and dumps it into circulation. This is one of the major causes of too much glucose in the blood. When Metformin lessens the amount of glucose put into the blood by the liver, the glucose level in the blood goes down. How Metformin actually does this is not known for sure. It may, in some way, improve insulin’s action on the liver cell.

The dose of Metformin is commonly three pills daily, spread throughout the day, though it varies with the individual.

Patients starting on Metformin typically experience diarrhea or nausea, and other symptoms of the stomach and bowels are possible. This can usually be avoided by starting with smaller doses, and increasing them slowly. Taking the pills in the middle of the meal also helps. In general, start by taking one pill in the middle of the biggest meal for 1-2 weeks, then take one pill with breakfast and one pill with supper daily for 2 weeks, then take one pill with each meal. Even building up slowly though, some people are still going to get stomach upset. It should be stressed that these side effects are generally short lived, lasting only several days. As you continue taking the pills, the side effects usually go away on their own. In the long run, only about 4% of people can’t tolerate the drug and must stop taking it.

Metformin should not be taken if radiologic dye is to be given. It should also not be given in the presence of severe liver or kidney problems, some severe heart problems, or if the patient is significantly dehydrated from any cause. Finally, it should not be taken during pregnancy.

Alpha-Glucosidase Inhibitors

Acarbose, available in Canada as Prandase, acts on the digestion — and therefore on the rate of absorption of food — resulting in a slower, more controlled delivery of glucose into the blood. The body can then better handle that glucose. Acarbose must be present in the intestine when the food arrives in order to work, so it should be taken immediately before eating.

This medication will cause some gas and bloating, and more rarely, diarrhea. This can be limited by increasing the doses very slowly. Tablets of 50 mg and 100 mg are available. Generally, this writer starts with 25 mg (i.e., ½ tablet) immediately before breakfast, for two weeks. After that, increase to 25 mg with breakfast and supper for two weeks, and then 25 mg with each meal for two weeks. Progress to 50 mg with breakfast, while staying at 25 mg with lunch and supper for two weeks. Then go to 50 mg with breakfast and supper, staying with 25 mg with lunch, for two weeks. Finally, progress to 50 mg with each meal. Even starting and increasing so slowly, passing gas remains a significant side effect and the individual must be patient for this to go away.

Acarbose should not be taken during pregnancy, but there are virtually no other circumstances that will have any problems. People with gastrointestinal problems that predispose them to gas or diarrhea should not take this medication if they cannot tell if the side effects are from the medication or from their bowel pathology.


The only one of this class of drugs currently on the Canadian market is Repaglinide (marketed as Gluconorm). Others will certainly be available in the relatively near future. This drug tells the pancreas to increase its output of insulin, but in a more physiological way than do the sulfonylureas. Its action is faster and has a shorter duration. This allows for greater insulin availability after eating, when it is most needed, and less insulin when it is not (allowing for fewer side effects of hypoglycemia). This is similar to what the non-diabetic pancreas would do.

The doses are highly variable and individual, and your doctor will advise you on the best dose for you. It should not be taken during pregnancy.


Canada currently has two drugs of this class on the market, Rosiglitazone (marketed as Avandia) and Pioglitazone (marketed as Actos).

Thiazolidinediones act on the cell nucleus to affect messages from DNA. These messages dramatically improve the action of insulin on the muscle cell, though it is not yet understood how. When insulin’s action is more effective, glucose has an easier time leaving the blood and entering the cell, and blood glucose levels go down. These drugs are very effective at lowering the glucose, when taken on their own or in combination with other pills or insulin.

There have been concerns about liver problems with the original thiazolidinedione, Troglitazone, which was available in the U.S. but never in Canada. This led to some caution with all of these drugs, and monitoring of liver function is recommended for all people who start on them. This should not scare the individual, as it would be very exceptional for any liver problem to occur with the drugs that are available.

Thiazolidinediones should not be taken by anyone with liver disease or severe heart disease, or by pregnant women.

The most common side effect is a mild swelling of the feet.


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