Type 2 diabetes is a progressive disease. Once we believed that changes in nutrition and an increase in physical activity would be enough to permanently keep blood glucose levels under control. Newer research is showing that Type 2 diabetes becomes harder to control over time. Although better nutrition and more physical activity are healthy choices at any time in life, as diabetes progresses it becomes more likely you will need medication to help reduce blood glucose levels. Insulin may also be needed for a short time during an illness or when pills can no longer keep blood glucose at acceptable levels. When people with diabetes need another medication or start insulin, it is not their fault. Type 2 diabetes worsens with time, but there are now more medications available than ever to keep blood glucose levels down.
The current medications to treat Type 2 diabetes work in three different areas.
Insulin resistance: This is the most important problem in Type 2 diabetes. Insulin is a hormone made by the pancreas, which allows glucose to reach your cells where it is used as energy. Insulin resistance prevents your body from using insulin effectively. Less glucose reaches the cells of the body and instead stays in the blood, causing high blood glucose.
Decreased insulin production: In diabetes the cells in the pancreas that make insulin don’t work properly and don’t put out insulin appropriately. This worsens with time. The longer you have diabetes, the less insulin is released from the pancreas. Less available insulin increases the amount of glucose in the blood, as insulin is required for glucose to leave the blood and reach the cells of the body.
Release of glucose stored in the liver: Your body stores extra glucose in the liver for times when you are not eating. It is released into the blood when your body senses your cells are not receiving enough glucose. With insulin resistance, your blood glucose levels are high, but glucose is not reaching your cells. This causes the release of glucose from liver stores, pushing blood glucose levels even higher.
We can divide medications used to lower blood glucose in Type 2 diabetes into three groups. Medications are grouped based on how they affect one of the three different areas. The groups of medications are insulin sensitizers, sugar/starch blockers, and insulin stimulators.
Insulin resistance occurs many years before Type 2 diabetes is diagnosed. Any decrease in insulin resistance will improve blood glucose levels. By decreasing insulin resistance, insulin sensitizers increase the effect of insulin on the cells of the body. More glucose can enter the cells to be used as energy and glucose is taken out of the blood. Insulin sensitizers can be used as a first medication with Type 2 diabetes.
Biguanides reduce the release of glucose from liver stores and increase the effect of insulin on the cells. Metformin (Glucophage™) is the only drug of this type. It is often the first medication used with Type 2 diabetes. It does not cause weight gain and may help with weight loss. Since 80 per cent of people with Type 2 diabetes are overweight, this can be helpful. Excess body weight can be linked to developing diabetes, and even a small loss of weight can decrease high blood glucose, blood pressure and cholesterol levels. Metformin does not cause low blood glucose levels when taken alone. Low blood glucose reactions can be dangerous for some people. Metformin would be a good choice if you have Type 2 diabetes and experience low blood glucose.
All medications can cause side effects. When first starting metformin, about one in five people get diarrhea, stomach upset or both. These effects are usually mild and only last a short period of time. Taking metformin with food and starting with a low dose can usually reduce these side effects. Metformin is also associated with a lowering of vitamin B12 levels when taken for two to three years. Ask your doctor to test your vitamin B12 levels if you have been on metformin this long.
Thiazolidinediones also make the body’s cells more sensitive to insulin’s effect. It may take two to three months before these drugs reach their full effectiveness. If a thiazolidinedione is added to another glucose-lowering drug, the dosage of that drug may need to be decreased as the thiazolidinedione reaches its full effect. If a drug that can cause low blood glucose is being taken, the possibility of a low blood glucose reaction increases as the thiazolidinedione starts to work.
Thiazolidinediones do not cause low blood glucose reactions alone. Rosiglitazone (Avandia™) and pioglitazone (Actos™) are examples of this type of insulin sensitizer. Your doctor will check your levels of liver enzymes every two months for the first year you are taking a thiazolidinedione. Side effects may include weight gain and fluid retention. People with heart disease should not take thiazolidinediones as fluid retention can worsen their condition. Report excessive weight gain or swelling of your legs to your doctor promptly.
Type 2 diabetes reduces the body’s ability to release enough insulin at the correct time to keep blood glucose levels under control. A healthy pancreas releases an appropriate amount of insulin after sugar (glucose) is absorbed from your food. With diabetes, less insulin is released. This causes your blood glucose levels to rise higher after eating. Sugar/starch blockers slow down the absorption of glucose from your food. Your pancreas then has more time to produce and release the insulin needed to deal with the food.
Sugar/starch blockers, also known as alpha-glucosidase inhibitors, lessen the rise in blood glucose after meals. They can be used as the first drug for treatment of Type 2 diabetes. Acarbose (Prandase™) is the only drug of this type available in Canada. Acarbose should be taken with the first bite of a meal to be most effective.
Acarbose should be started at a low dose and slowly increased to reduce the chance of gas, diarrhea and abdominal pain. Your body adjusts to the action of acarbose, so these side effects decrease with time. Acarbose does not cause low blood glucose when used by itself. If acarbose is taken with a drug that can cause low blood glucose and this occurs, it should be treated with dextrose tablets. Skim milk may also be used. When you are taking acarbose, low blood glucose will not improve with the type of sugar found in pop, juice or candy.
In Type 2 diabetes the cells in the pancreas that would normally make insulin do not work as well as they should, resulting in too little insulin being produced. Insulin stimulators cause these cells to release more insulin. More insulin allows the body’s cells to take up more glucose from the blood and decreases blood glucose levels.
Sulfonylureas cause the pancreas to produce more insulin. Glyburide (Diabeta™) and gliclazide (Diamicron™) are the most commonly used drugs of the sulfonylureas. Tolbutamide and chlorpropamide are now rarely used. Glimepiride (Amaryl™) is the newest sulfonylurea available. These drugs are often used in combination with insulin sensitizers. Since both types of drugs reduce blood glucose levels in different ways, using them together can lower blood glucose levels further.
Sulfonylureas can cause low blood glucose levels alone or in combination with other drugs. Learn the symptoms of a low blood glucose reaction and how to treat one. When you take sulfonylureas, you must not skip meals or stop eating on sick days. If you cannot eat solid foods, juice or pop can provide sugar to prevent low blood glucose reactions. Develop a sick day plan with the help of your doctor or diabetes educator. Sulfonylureas may also cause stomach upset or weight gain. Taking them with food can decrease stomach upset. If you are allergic to sulpha drugs, you may not be able to take sulfonylureas.
Meglitinides also increase the production of insulin by cells in the pancreas. Nateglinide (Starlix™) and repaglinide (GlucoNorm™) are the meglitinides currently available. These drugs reduce the blood glucose levels after meals more quickly than sulfonylureas. Take them before each meal. If you skip a meal, you should skip the pill you would take before that meal. Meglitinides are an option for people who cannot take sulfonylureas.
Repaglinide can cause low blood glucose reactions, but reactions are much less likely with nateglinide. Headache, chest infections, and joint pain can occur with either medication. Chest pain can occur with repaglinide, and should be reported to your doctor.
As Type 2 diabetes progresses, medications you take by mouth may become less effective in lowering high blood glucose levels. Treatment of your Type 2 diabetes may have begun by changing your nutrition and physical activity. You may have started with a single pill and had more added over time. If medications taken by mouth are no longer effective for you, your diabetes has progressed and insulin needs to be added. This doesn’t happen because you haven’t cared for yourself properly.
Over time, everyone’s diabetes may get worse. Insulin can very quickly bring your blood glucose levels down to an acceptable level. It can be added to drugs you are already taking or used alone. With proper training, using insulin can be as easy as taking a pill. When blood glucose levels are reduced, studies show that long-term complications from diabetes are reduced and people with diabetes live longer, healthier lives. Insulin is also the only choice for a woman with Type 2 diabetes who becomes pregnant. Pills to reduce blood glucose cannot be taken during pregnancy.
It is important to continue to be physically active, eat well, and take your medications regularly. With more medications becoming available to treat Type 2 diabetes, blood glucose levels can now be controlled more easily. You and your doctor have more choices of medications to treat your diabetes. Medications can also be chosen based on your stage of diabetes. Each new study brings us more understanding about the nature of diabetes and how to treat it. Ask your pharmacist for more information about your medications and the new drugs available for Type 2 diabetes. Discuss medication selection with your doctor, and get involved in monitoring how your medications are working for you.
Medications to Lower Blood Glucose in Type 2 Diabetes
|Insulin Sensitizers||Decrease insulin resistance||Glucophage™ (metformin), Avandia™ (rosiglitazone), Actos™ (pioglitazone)|
|Sugar/Starch Blockers||Slow absorption
|Insulin stimulators||Increase insulin production||Diabeta™ (glyburide), Diamicron™ (gliclazide), GlucoNorm™ (repaglinide), Starlix™ (nateglinide)|