Medications for Type 2 Diabetes
Note: This is the first part of a two-part series. The second part will appear in the February 2005 issue of Diabetes Health.
In 1942, a scientist studying a sulfa drug (antibiotic) for typhoid fever found that the drug caused an unexpected side effect in malnourished patients—hypoglycemia. Studies of these (sulfonylureas) compounds ultimately led to the first oral medication for diabetes, tolbutamide (marketed as Orinase).
Orinase, like all sulfonylureas, works by stimulating the beta cells of the pancreas to make additional insulin. This type of drug can be used only in type 2 diabetes since it requires functioning pancreatic beta cells that produce insulin to work. Orinase and the other so-called “first generation” sulfonylurea drugs (Diabenese, Dymelor and Tolinase), although still available, are generally no longer used in the United States.
Today, almost all patients who need a sulfonylurea are prescribed one of three so-called second-generation sulfonylurea drugs:
- Glyburide (Micronase, Glynase, or Diabeta)
- Glipizide (Glucotrol, Glucotrol XL)
- Glimepiride (Amaryl)
Sulfonylureas are taken once or twice a day and may remain effective for 24 hours or longer. They can be given with other drugs for diabetes. They are also present in two newer oral agent combination drugs, Glucovance (glyburide plus metformin) and Metaglip (glipizide plus metformin). Glyburide lasts longer and has been associated with more hypoglycemia than the other two.
In my own practice, I avoid glyburide, especially in the elderly, who are more prone to hypoglycemia.
Another potential problem with this group of drugs is allergies. Patients who are allergic to the sulfa antibiotics may also be allergic to these drugs. They may develop a mild (or possibly a serious) skin rash, requiring them to stop taking the drug. Another side effect of these drugs is weight gain. Eating less, exercising more and cutting back the dose of the drug can minimize weight gain.
The main side effect with all medications of this class is hypoglycemia (low blood glucose), usually occurring three or more hours after the last meal.
Hypoglycemia is most likely to occur during and after physical activity or when patients
- skip or delay meals
- are malnourished
- drink alcohol
- have impaired function of kidney or liver
- have a gastrointestinal disease (such as food poisoning)
- take other drugs (sulfa drugs, Coumadin, Lopid, high-dose aspirin)
- are begun on other diabetes drugs (metformin, Actos, Avandia, insulin)
Antihyperglycemic Agents for Type 2 Diabetes and Site of Action
3 Mechanisms and
6 Different Drug Classes
INCREASE INSULIN LEVELS
- Sulfonylureas (pancreatic beta cells)
- Meglitinides and Phenylalanine derivatives (pancreatic beta cells)
INCREASE INSULIN SENSITIVITY
- Biguanides (liver)
- Thiazolidinediones (muscle)
DELAY CARBOHYDRATE ABSORPTION
- Alpha-Glucosidase Inhibitors (small intestine)
Feb 1, 2005