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Understanding Oral Diabetes Medications

by Gail Brashers-Krug

Today, almost 21 million Americans have diabetes, and more than 90 percent of those have type 2, or insulin resistant diabetes. Doctors often prescribe oral medications to treat type 2 diabetes, either alone or combination with insulin therapy. This article provides a guide to those oral medications.

Which Diabetics Use Pills?
With a few exceptions, diabetes comes in two types. Type 1 diabetes occurs when the body does not produce enough insulin on its own. To treat type 1, you must restore the proper amount of insulin—either by taking insulin (through injection or inhalation), or by receiving a transplant, either of an entire pancreas or of specialized pancreas cells, called islet cells. Type 1 cannot be treated with oral medications.

Type 2 diabetes occurs when the body produces enough insulin, but gradually becomes insulin resistant—that is, loses the ability to process insulin. Type 2 is usually controlled first through diet and exercise, which improve your body’s ability to process its insulin. For most type 2 diabetics, however, diet and exercise changes are not enough. The next step is oral diabetes medication. Moreover, most type 2 diabetics eventually stop producing enough insulin, and often cease insulin production altogether. As a result, many type 2 diabetics will ultimately need insulin therapy in combination with their pills.

How Do the Different Pills Work?
Oral diabetes medications attack the problem in three ways.

More insulin: Some pills stimulate your pancreas to produce more insulin. The first successful “diabetes pills” were the sulfonylureas (glyburide, glipizide, glimepiride, tolazamide, chlorpropamide, and tolbutamide). These are insulin secretagogues, that is, chemicals that cause your pancreas to produce more insulin. When you take these medications, your body is still not processing insulin as effectively as it should, but there is more of it in your bloodstream to process.

More recently, another group of oral medications have been developed that, like the sulfonylureas, stimulate increased insulin production. These medicines, called by the brand names Prandin and Starlix, are more effective than the first generation of drugs, but they accomplish the same purpose—that is, they overcome insulin resistance by increasing insulin supply.

The obvious problem with the insulin-increasing medications is that they can cause hypoglycemia, or low blood sugar. In addition, insulin secretagogues become useless when the pancreas ceases insulin production, as it eventually does in many type 2 diabetics. At that point, insulin must be injected.

Using insulin better: Newer diabetes medications attack type 2 at its source: “insulin resistance,” the body’s increasing inability to use insulin. Drugs known as TZD’s (trade names Actos and Avandia) directly attack the problem, making the body (temporarily) more sensitive to insulin action. These medicines can be prescribed alone, with the sulfonylureas, or in a “compound” medication like Avandamet (Avandia and Metformin). TZD’s help the type 2 diabetic make better use of the insulin he or she still produces. They are useless where insulin is not present; they are not a substitute for insulin.

The TZD’s, Actos and Avandia, have recently caused concern in scientific circles because they may increase the risk of heart attack for patients who already have heart failure. As a result of that concern, the FDA held hearings, and required that the drugs carry a boxed warning stating that they are unsuitable for patients with heart failure.

Less glucose: A third category of medicines, including the widely-prescribed metformin, stimulates the liver to produce less glucose, and/or temporarily suppress the digestive enzymes that turn carbohydrates into glucose, slowing digestion and glucose absorption, keeping glucose levels more even. More a dietary management tool than antidote to insulin shortage, these medicines help some diabetics keep a more stable blood glucose level, and avoid post-meal spikes. Unfortunately, they can have many side effects, and are less than universal in their utility.

What About Using Pills and Insulin Together?
Unfortunately, oral medications alone often cannot control diabetes. Many type 2 diabetics, diagnosed as young adults, at first successfully control their condition with diet and exercise, but find they need the pills as they grow older. A number of years (and dosage increases) later, these diabetics have reached the limit of what oral medications can do for them, and need to start injecting insulin to keep their blood glucose at a safe level.

Psychological insulin resistance: When one’s blood glucose levels and A1c values begin to climb, despite diabetes pills, it is time to begin injecting insulin. But many diabetics just do not want to take that step—an attitude health care professionals call “psychological insulin resistance.” Some of this is plain old fear of sticking yourself with needles—nurtured by memories from our childhood in the bad old days of dull-as-nails reusable syringes! But some doctors contribute to the problem when they don’t make it clear to the patient why staying with oral medications is no longer working. Staying on the now-ineffective pills means that blood glucose will be out of control. Poorly controlled glucose leads to heart disease, stroke, blindness, kidney failure, neuropathy, and even amputation. Even worse, some doctors assume their patients do not want to begin regular insulin injections, so they don’t even suggest it. The risks of remaining on oral diabetes medications once the pancreas has ceased producing insulin are far greater than the risks of taking insulin.

Once your doctor has decided to implement an insulin regimen, he or she may still keep you on oral medications, or change the dosages, or stop certain medications altogether. For many type 2 diabetics, a combination of oral medication and insulin therapy is the most effective way to control their diabetes and delay or even prevent the onset of complications.

Inhaled insulin: Last year saw the introduction of Exubera, an inhalable insulin. For the first time, we have insulin that does not require injection. But there are problems. First, Exubera is fast-acting insulin, with a response curve quite similar to that of Humalog. There are no longer-acting, inhalable insulins, yet. Another problem is high cost. Exubera does what fast injected insulins do, without the needle-stick, but at about twice the price. Your insurance may or may not accept that cost.

There is also a third category of diabetes medicine, neither oral pills nor insulin. It is called Byetta, a medicine injected twice a day, and made from a synthetic form of Gila monster saliva. Seriously! Byetta’s active ingredient, exenatide, works by mimicking the effects of a human hormone called GLP-1, which is normally released after meals, stimulating digestion and insulin production. GLP-1 also discourages the liver from producing too much sugar. Byetta has one highly touted side effect: it can cause significant weight loss. Unfortunately, however, it can also cause severe nausea.

It is now far easier for you and your doctor to tailor your diabetes medications, whether oral or injectible, with or without insulin, to your specific needs—improving your control and lessening your possibility of serious complications.

The new FDA warning accompanying Actos and Avandia states they should not be taken by patients with “heart failure.” Keep in mind that “heart failure” is NOT the same thing as a heart attack. Heart failure means that the heart can’t pump enough blood to the body’s other organs. You can have a heart attack without having heart failure, and you can have heart failure without having a heart attack. If you have had any heart trouble, please check with your doctor to make sure that you do not have heart failure.

Brand name
(generic name)
How It Works
Other Information

Amaryl (glymepiride)
Diabinese (chlorpropamide)
Micronase (glyburide)
Glynase (glyburide)
DiaBeta (glyburide)
Glucotrol (glipizide)

Sulfonylureas Increases insulin secretion May cause hypoglycemia
Prandin (repaglinide) Meglitinide Increases insulin secretion May cause hypoglycemia
Starlix (nateglinide) Phenylalanine derivative Increases insulin secretion May cause hypoglycemia
Avandia (rosiglitazone maleate) TZD Helps cells respond more effectively to insulin Cannot be used in patients with heart failure
Actos (pioglitazone HCl) TZD Helps cells respond more effectively to insulin Cannot be used in patients with heart failure
Glucophage (metformin) Biguanide Decreases the liver’s glucose production Most commonly prescribed diabetes drug
Riomet (metformin in liquid form) Biguanide Decreases the liver’s glucose production Liquid form of the most commonly prescribed diabetes drug
Precose (acarbose) Alpha-glucosidase inhibitor Slows intestinal absorption of some carbohydrates Works best when taken with the first bite of food
Glyset (miglitol) Alpha-glucosidase inhibitor Slows intestinal absorption of some carbohydrates Works best when taken with the first bite of food

Gail Brashers-KrugAbout the Author
Gail Brashers-Krug, JD, is Director of Special Projects for the Diabetes Action Network. A mother of five and a recovering trial lawyer, Gail works with the diabetes industry, diabetes advocacy groups, and government agencies to advocate on behalf of diabetics with complications.