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Over the past seven years, the number of oral drug therapies for the treatment of type 2 diabetes has dramatically increased. Of the six basic types of medication that can help normalize your blood glucose, five are available as oral drugs.
The sixth type of medication is insulin, which is available today only in injectable form or for use in an insulin pump. (Insulin may become available in the future as an inhaled formulation, however, and other forms are also in development.)
This article focuses on the various categories of oral drugs currently available and used by people with type 2 diabetes. None of these oral drugs for diabetes are approved for use during pregnancy or breastfeeding.
You and your physician should work together to determine which oral agent or combination of agents is best for you. By understanding how your medications work, you can feel more comfortable and confident in controlling your blood glucose.
Sulfonylureas work by stimulating the pancreas to produce insulin.
Historically, doctors have preferred to start a person with newly diagnosed type 2 diabetes on a sulfonylurea (in addition to diet and exercise). Today, however, if you are newly diagnosed, your physician might start you either on a sulfonylurea or on one of the other four types of oral drugs.
Although the chart on pages 46-47 does not list every sulfonylurea available, it does provide information on three of the most widely used: glyburide (DiaBeta, Micronase, Glynase), glimepiride (Amaryl) and glipizide (Glucotrol).
Sulfonylureas work well either as a single therapy or when combined with other oral agents and/or insulin.
Hypoglycemia (low blood glucose) and weight gain are the most common side effects experienced by people taking sulfonylureas.
This category includes repaglinide (Prandin) and nateglinide (Starlix).
Meglitinides work similarly to sulfonylureas, in that they also increase insulin production by the pancreas, although they tend to work more quickly than the sulfonylureas and for a shorter duration. Because sulfonylureas and meglitinides both work by stimulating the pancreas to produce more insulin, they are not used in combination.
Because meglitinides work so quickly, they must be taken immediately before each meal. If you are skipping a meal, you must also skip that dose of the meglitinide.
Possible side effects of these medications include hypoglycemia and weight gain, though the meglitinides are less likely than sulfonylureas to cause either of these side effects. Meglitinides are ideal agents for people who have erratic eating schedules, for those who do not have trouble remembering to take them before each meal and for those who may have had episodes of low blood glucose with sulfonylureas.
Like sulfonylureas, meglitinides can be combined with other anti-diabetes medications. For example, meglitinides and metformin (Glucophage) are commonly used together.
The only biguanide available in the United States is metformin (Gluco-phage).
Metformin, which is now also available in generic forms, does not work in the same way as sulfonylureas or meglitinides.
Derived from the French lilac plant, metformin normalizes blood-glucose levels by reducing the liver's glucose production. Aside from its blood-glucose normalizing properties, metformin also tends to improve lipid abnormalities common in persons with type 2 diabetes. Metformin has been shown to lower triglyceride levels, decrease LDL ("bad") cholesterol and increase HDL ("good") cholesterol. Metformin does not cause weight gain.
When used as a sole therapy, metformin does not tend to cause hypoglycemia. When it is used with insulin, sulfonylureas, or meglitinides, however, hypoglycemia is more likely.
The most common side effects of metformin are gastrointestinal in nature (bloating, nausea and diarrhea), but symptoms often subside with continued therapy. Taking metformin with food helps to minimize these symptoms.
Only people with normal kidney function should take this drug. A serum creatinine laboratory test result should be less than 1.4 mg/dl for women and less than 1.5 mg/dl for men to provide adequate kidney clearance of metformin.
Use of metformin can result in a very rare but serious complication, called lactic acidosis. Lactic acidosis occurs most often in people who do not have normal kidney function, and up to half of cases are fatal. Signs of lactic acidosis include feeling very weak, tired or uncomfortable; experiencing unusual muscle pain, trouble breathing, or unusual stomach discomfort; feeling cold, dizzy or lightheaded; or suddenly developing a slow or irregular heart beat. If you are using metformin and your medical condition suddenly changes, you should contact a physician right away.
Caution is advised for people over 80 years old unless there is laboratory evidence of normal creatinine clearance. People taking medication for congestive heart failure should also be cautious when taking metformin. Metformin is contraindicated for individuals who drink alcohol excessively and for individuals who are hospitalized or undergoing medical tests or procedures using intravenous iodinated dyes.
Overweight individuals, those with lipid abnormalities and people with insulin resistance often experience a good response to metformin. Met-formin can be used in combination with other diabetes therapies.
This category includes acarbose (Precose) and miglitol (Glyset). Alpha-glucosidase inhibitors work by slowing down the digestion of consumed carbohydrates.
These agents tend to lower post-meal rises in blood glucose. They must be taken with the first bite of food. Like metformin, the alpha-glucosidase inhibitors do not tend to cause hypoglycemia.
Potential side effects include flatulence, diarrhea and abdominal pain, symptoms that often subside with continued therapy. People with a history of significant gastrointestinal disease (inflammatory bowel disease, ulcers of the colon, or gastrointestinal obstruction) should not take alpha-glucosidase inhibitors.
When alpha-glucosidase inhibitors are used in combination with insulin, meglitinides or sulfonylureas, hypoglycemia can occur and needs to be treated with pure glucose (tablets or gel) or milk since Precose and Glyset delay the absorption of other carbohydrates.
People who experience post-meal hyperglycemia (high blood glucose) are excellent candidates for treatment with an alpha-glucosidase inhibitor.
Thiazolidinediones (‘Glitazones,’ ‘TZDs’)
The thiazolidinediones, commonly referred to as "glitazones" or "TZDs," make up the final category of oral agents. This group includes both pioglitazone (Actos) and rosiglitazone (Avandia).
The glitazones work by increasing the sensitivity of your muscle cells to the action of insulin. They are therefore known as "insulin sensitizers," which means that they decrease insulin resistance. They may take up to four or six weeks to reach maximum effectiveness.
When your muscles become more sensitive to insulin, the glucose in your bloodstream is more easily transported into your muscle cells, where it is eventually stored as glycogen—a carbohydrate stored in the muscles and liver and used as energy during exercise. Actos has also been shown to decrease triglyceride levels.
Generally, people with congestive heart failure should use TZDs only with caution or not at all. Only people with normal liver function should use TZDs. Liver function tests are advised before starting and then every two months for the first year.
Potential side effects include edema and/or weight gain. If you experience either symptom, you should contact your physician. People most likely to respond to the glitazones include those with insulin resistance.
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