[Extracted from American Diabetes Association]
In people with diabetes, blood glucose levels are too high. These high levels occur because glucose remains in the blood rather than entering cells, where it belongs. But for glucose to pass into a cell, insulin must be present and the cell must be "hungry" for glucose.
People with type 1 diabetes don't make insulin. For them, insulin shots are the only way to keep blood glucose levels down.
People with type 2 diabetes tend to have two problems : they don't make quite enough insulin and the cells of their bodies don't seem to take in glucose as eagerly as they should.
All diabetes pills sold today in the United States are members of five classes of drugs : sulfonylureas (Glicazide), meglitinides, biguanides (Metformin), thiazolidinediones, and alpha-glucosidase inhibitors. These five classes of drugs work in different ways to lower blood glucose levels.
Sulfonylureas
Sulfonylureas stimulate the beta cells of the pancreas to release more insulin. Sulfonylurea drugs have been in use since the 1950s. Chlorpropamide (brand name Diabinese) is the only first-generation sulfonylurea still in use today. The second generation sulfonylureas are used in smaller doses than the first-generation drugs. There are three second-generation drugs: glipizide (brand names Glucotrol and Glucotrol XL), glyburide (Micronase, Glynase, and Diabeta), and glimepiride (Amaryl). These drugs are generally taken one to two times a day, before meals. All sulfonylurea drugs have similar effects on blood glucose levels, but they differ in side effects, how often they are taken, and interactions with other drugs.
Meglitinides
Meglitinides are drugs that also stimulate the beta cells to release insulin. Repaglinide (brand name Prandin) and nateglinide (Starlix) are meglitinides. They are taken before each of three meals.
Because sulfonylureas and meglitinides stimulate the release of insulin, it is possible to have hypoglycemia (low blood glucose levels).
You should know that alcohol and some diabetes pills may not mix. Occasionally, chlorpropamide, and other sulfonylureas, can interact with alcohol to cause vomiting, flushing, or sickness. Ask your doctor if you are concerned about any of these side effects.
Biguanides
Metformin (brand name Glucophage) is a biguanide. Biguanides lower blood glucose levels primarily by decreasing the amount of glucose produced by the liver. Metformin also helps to lower blood glucose levels by making muscle tissue more sensitive to insulin so glucose can be absorbed. It is usually taken two times a day. A side effect of metformin may be diarrhea, but this is improved when the drug is taken with food.
Thiazolidinediones
Rosiglitazone (Avandia) and pioglitazone (ACTOS) are in a group of drugs called thiazolidinediones. These drugs help insulin work better in the muscle and fat and also reduce glucose production in the liver. The first drug in this group, troglitazone (Rezulin), was removed from the market because it caused serious liver problems in a small number of people. So far rosiglitazone and pioglitazone have not shown the same problems, but users are still monitored closely for liver problems as a precaution. Both drugs appear to increase the risk for heart failure in some individuals, and there is debate about whether rosiglitazone may contribute to an increased risk for heart attacks. Both drugs are effective at reducing A1C and generally have few side effects.
DPP-4 Inhibitors
A new class of medications called DPP-4 inhibitors help improve A1C without causing hypoglycemia. They work by by preventing the breakdown of a naturally occuring compound in the body, GLP-1. GLP-1 reduces blood glucose levels in the body, but is broken down very quickly so it does not work well when injected as a drug itself. By interfering in the process that breaks down GLP-1, DPP-4 inhibitors allow it to remain active in the body longer, lowering blood glucose levels only when they are elevated. DPP-4 inhibitors do not tend to cause weight gain and tend to have a neutral or positive effect on cholesterol levels. Sitagliptin (Januvia) is currently the only DPP-4 inhibitor on the market.
Alpha-glucosidase inhibitors
Acarbose (brand name Precose) and meglitol (Glyset) are alpha-glucosidase inhibitors. These drugs help the body to lower blood glucose levels by blocking the breakdown of starches, such as bread, potatoes, and pasta in the intestine. They also slow the breakdown of some sugars, such as table sugar. Their action slows the rise in blood glucose levels after a meal. They should be taken with the first bite of a meal. These drugs may have side effects, including gas and diarrhea.
Oral combination therapy
Because the drugs listed above act in different ways to lower blood glucose levels, they may be used together. For example, a biguanide and a sulfonylurea may be used together. Many combinations can be used. Though taking more than one drug can be more costly and can increase the risk of side effects, combining oral medications can improve blood glucose control when taking only a single pill does not have the desired effects. Switching from one single pill to another is not as effective as adding another type of diabetes medicine.
Can diabetes pills help me ?
Only people with type 2 diabetes can use pills to manage their diabetes. These pills work best when used with meal planning and exercise. This way you have three therapies working together to lower your blood glucose levels.
Diabetes pills don't work for everyone. Although most people find that their blood glucose levels go down when they begin taking pills, their blood glucose levels may not go near the normal range.
What are the chances that diabetes pills will work for you ? Your chances are low if you have had diabetes for more than 10 years or already take more than 20 units of insulin each day. On the other hand, your chances are good if you developed diabetes recently or have needed little or no insulin to keep your blood glucose levels near normal.
Diabetes pills sometimes stop working after a few months or years. The cause is often unknown. This doesn't mean your diabetes is worse. When this happens, oral combination therapy can help.
Even if diabetes pills do bring your blood glucose levels near the normal range, you may still need to take insulin if you have a severe infection or need surgery. Pills may not be able to control blood glucose levels during these stressful times when blood glucose levels shoot up.
Also, if you plan to become pregnant, you will need to control your diabetes with diet and exercise or with insulin. It is not safe for pregnant women to take oral diabetes medications.
There is no "best" pill or treatment for type 2 diabetes. You may need to try more than one type of pill, combination of pills, or pills plus insulin.
What about insulin ?
Although it is a common practice to try pills before insulin, you may start on insulin based on several factors.
These factors include :
how long you have had diabetes;
how high your blood glucose level is;
what other medicines you take;
your overall health;
Because diabetes pills seem to help the body use insulin better, some people take them along with insulin shots. The idea behind this "combination" therapy is to try to help insulin work better.
Using diabetes medications wisely
In general, diabetes pills are safe and work well. But like any other drug, they must be used with care.
All diabetes pills can interact with other medicines. Because of the chance of medication interactions, you need to tell your doctor about all medicines you are taking. While you're taking diabetes pills, you should check with your doctor even before starting anything new -- even over-the-counter items.
Any sulfonylurea or meglitinide can cause blood glucose levels to drop too low (hypoglycemia). Metformin or the glitazones rarely cause hypoglycemia unless taken with insulin stimulators (sulfonylureas or repaglinide) or insulin injections. Acarbose or meglitol, taken as prescribed, does not cause hypoglycemia. However, hypoglycemia can occur when acarbose or meglitol is taken in combination with other oral diabetes medications.
Two new injectable drugs have recently been approved by the FDA
Pramlintide (brand name Symlin) is a synthetic form of the hormone amylin, which is produced along with insulin by the beta cells in the pancreas. Amylin, insulin, and another hormone, glucagon, work in an interrelated fashion to maintain normal blood glucose levels.
Pramlintide injections taken with meals have been shown to modestly improve A1C levels without causing increased hypoglycemia or weight gain and even promoting modest weight loss. The primary side effect is nausea, which tends to improve over time and as an individual patient determines his or her optimal dose.
Because of differences in chemistry, pramlintide cannot be combined in the same vial or syringe with insulin and must be injected separately. Pramlintide has been approved for people with type 1 diabetes who are not achieving their goal A1C levels and for people with type 2 diabetes who are using insulin and are not achieving their A1C goals.
Exenatide (brand name Byetta) is the first in a new class of drugs for the treatment of type 2 diabetes called incretin mimetics. Exenatide is a synthetic version of exendin-4, a naturally-occurring hormone that was first isolated from the saliva of the lizard known as a Gila monster. Exenatide works to lower blood glucose levels primarily by increasing insulin secretion. Because it only has this effect in the presence of elevated blood glucose levels, it does not tend to increase the risk of hypoglycemia on its own, although hypoglycemia can occur if taken in conjunction with a sulfonylurea. The primary side effect is nausea, which tends to improve over time.
Like pramlintide, exenatide is injected with meals and, as with pramlintide, patients using exenatide have generally experienced modest weight loss as well as improved glycemic control. Exenatide has been approved for use by people with type 2 diabetes who have not achieved their target A1C levels using metformin, a sulfonylurea, or a combination of metformin and a sulfonylurea.
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