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Oral Medicines for Type 2 Diabetes

by Patti Geil, M.S., R.D., C.D.E., and Laura Hieronymus, M.S.Ed., A.P.R.N., B.C.-A.D.M., C.D.E.

Taking care of your diabetes is a bit like building a home. With input from your diabetes care team contractors, you begin by drafting a well-thought-out set of blueprints and assembling all the tools you need to control your blood glucose levels. Healthy eating and physical activity serve as a sturdy foundation for your house of diabetes care, while monitoring blood glucose provides you with feedback for changes to the existing plans.

Although eating well and exercising are always the first line of therapy for all types of diabetes, there may come a time when you and your health-care team decide to intensify your Type 2 diabetes control by adding an oral blood-glucose-lowering medicine to your carefully crafted plan. Oral medicines are one tool that can give you a step up toward reaching your blood glucose targets and reinforcing your strong diabetes home.

What goes wrong

Type 2 diabetes is a complex condition, which means there are a multitude of options for successful treatment. In a person without diabetes, blood glucose rises whenever food is eaten. The pancreas quickly senses the glucose and produces insulin, which opens the doors of the muscle and fat cells so the glucose can be used for energy. People with Type 2 diabetes may release the proper amount of insulin in response to glucose, but the cells are “insulin resistant”; that is, they can’t sense the insulin and don’t take in much glucose. This leaves glucose in the bloodstream, which stimulates the pancreas to produce more insulin than would normally be necessary. Over the course of years, the pancreas may fail to keep up with the demand for insulin, leading to persistently elevated blood glucose levels and a diagnosis of Type 2 diabetes.

The liver is also involved in the process by tracking insulin levels in the blood. In a person without diabetes, both insulin and glucose levels are elevated at the same time after eating. If a person hasn’t eaten for several hours (such as overnight), the liver senses the lack of insulin and responds by producing glucose from storage to keep the blood glucose level from dropping too low. When Type 2 diabetes sets in, the liver may fail to sense insulin levels properly and may produce more glucose than required.

In a nutshell, three areas “in need of repairs” characterize Type 2 diabetes: insulin resistance (muscle cells that don’t easily take in glucose), insulin deficiency (a pancreas that doesn’t make enough insulin), and increased hepatic glucose output (a liver that releases too much glucose). Fortunately, there are several options in the diabetes toolbox to make the needed repairs, including healthy eating, physical activity, and oral medicines.

The diabetes toolbox

Keeping blood glucose levels near to normal can reduce your risk of the chronic or long-term complications of diabetes such as retinopathy (eye disease), nephropathy (kidney disease), neuropathy (nerve damage), and cardiovascular disease. You and your health-care team should work together to draw up the blueprints for successfully reaching your individualized target blood glucose goals.

Many health-care providers and their patients choose to begin the path to intensified blood glucose control with oral medicines. It’s important to note up front that oral medicines are not insulin. Insulin can’t be given orally because digestive enzymes would destroy it. Control of Type 2 diabetes involves a stepwise approach that begins with identifying the proper treatment plan based on your age, weight, desired level of blood glucose control, and specific characteristics of the medicines being considered.

Often the plan begins with monotherapy, which is one blood-glucose-lowering medicine in addition to a healthy lifestyle. If this doesn’t achieve the desired result, adding one or more additional medicines (combination therapy) may be considered. Combination therapy may involve taking two or more individual pills, or it may be achieved with one of the newer combination pills, which have two drugs in one pill.

Research has shown that most of the oral diabetes medicines currently on the market lower glycosylated hemoglobin (HbA1c) approximately 1% to 2%. The HbA1c test is an indicator of average blood glucose control over the previous 2–3 months. The American Diabetes Association currently advocates an HbA1c reading lower than 7% for most people with diabetes. The American Academy of Clinical Endocrinologists recommends an HbA1c value below 6.5%. You and your health-care provider should agree on a target that is right for you. Higher HbA1c levels are associated with the development of diabetes complications.

In general, certain classes of drugs, including the sulfonylureas, meglitinides, d-phenylalanine derivatives, and biguanides, are more potent in lowering blood glucose than are others, such as the thiazolidinediones or alpha-glucosidase inhibitors when used as monotherapy. (See “Effectiveness of Oral Medicines” for a comparison.) However, there are limits to how much of any one drug can be taken. When a maximal dose of one drug isn’t enough to keep blood glucose levels in the desired range, adding a drug from a different class can lower blood glucose further.

Insulin injections are another option for treating Type 2 diabetes and may eventually be necessary due to its progressive nature. Many physicians recommend starting insulin when three oral medicines are not effective at keeping blood glucose under control. Insulin may either be added to the current regimen of pills or used in place of one or more of the oral medicines a person has been taking.

Type 2 diabetes involves several problems in metabolism, and oral medicines have been developed to provide solutions to each one. Six distinct classes of oral drugs are now available for the treatment of Type 2 diabetes. “Oral Diabetes Medicines at a Glance” summarizes the important characteristics of each class. Each class has a different mechanism of action, which means that each contributes to blood glucose control in a different way.

Alpha-glucosidase inhibitors. This class of drugs, which includes acarbose (brand name Precose) and miglitol (Glyset), acts by inhibiting the breakdown and subsequent absorption of carbohydrates from the gut following meals, so it is most effective in controlling postprandial (after-meal) elevations in blood glucose.

Hypoglycemia (low blood glucose) generally does not occur when one of these pills is taken as monotherapy, but it can occur when one or the other is taken in combination with a blood-glucose-lowering drug that can cause hypoglycemia. It’s important to note that because of the carbohydrate-blocking effect of alpha-glucosidase inhibitors, some traditional treatments for low blood glucose, such as fruit juice, aren’t as effective at raising blood glucose as they normally would be. Sources of pure glucose, such as tablets or gel, are recommended. Gastrointestinal side effects such as abdominal discomfort, bloating, flatulence, and diarrhea may occur when using an alpha-glucosidase inhibitor.

Biguanides. Only one biguanide, namely metformin (Glucophage), is currently approved for marketing in the United States. Metformin is most effective in overweight or obese people who are insulin-resistant. It works by reducing liver glucose output, and it may also improve insulin sensitivity in the liver and muscle and fat cells. Metformin appears to suppress appetite and also lower cardiovascular risk factors without risk of hypoglycemia. Its major disadvantage is that it can cause gastrointestinal problems, particularly at higher doses.

A rare but serious side effect of metformin is lactic acidosis, in which lactic acid builds up in the bloodstream. People with heart, lung, kidney, or liver problems and those who drink alcohol heavily are more prone to developing lactic acidosis.

Sulfonylureas. This class of drugs—which includes glipizide (Glucotrol, Glucotrol XL), glyburide (DiaBeta, Glynase, Micronase), glimepiride (Amaryl), and the less commonly used chlorpropamide (Diabinese), tolazamide (Tolinase), and tolbutamide (Orinase)—works most successfully in those who have recently been diagnosed with Type 2 diabetes. Sulfonylureas are “pancreas stimulators” that cause the beta cells to release more insulin. They are generally inexpensive, and they reduce fasting blood glucose levels effectively. Side effects associated with their use include weight gain and hypoglycemia.

Meglitinides and d-phenylalanine derivatives. There is one meglitinide on the market, repaglinide (Prandin), and one d-phenylalanine derivative, nateglinide (Starlix). These drugs are not sulfonylureas, but their mechanism of action closely resembles them. They stimulate the release of insulin from pancreatic beta cells, but they take effect more quickly, and their effects last for only a short amount of time. They are also most effective in people recently diagnosed with Type 2 diabetes, and they act to control postprandial blood glucose elevations.

Either drug should be taken immediately before a meal; if you skip a meal, don’t take a pill or you will risk hypoglycemia. If you have trouble maintaining a regular eating pattern, you may have a problem remembering to take these pills.

Thiazolidinediones. Thiazolidinediones, often referred to as TZDs or glitazones, are insulin sensitizers, designed to help insulin work better in muscle and fat tissue while protecting insulin-producing beta cells from further damage. The first approved drug in this class, troglitazone (Rezulin), was removed from the market in 2000 because of reports of severe liver toxicity. The currently available TZDs, pioglitazone (Actos) and rosiglitazone (Avandia), have not been associated with this problem. Nonetheless, periodic liver function tests are still recommended for people taking either pioglitazone or rosiglitazone.

Because the TZDs don’t increase insulin secretion, they do not carry the risk of hypoglycemia. People who already use insulin may find that adding a TZD to their diabetes regimen may help to significantly reduce their daily insulin requirement. However, TZDs are costly, and significant weight gain has been reported with their use.

Special considerations

Oral blood-glucose-lowering medicines are generally not recommended for use in Type 1 diabetes because of the total lack of pancreatic insulin production that characterizes this condition. However, research has shown that the alpha-glucosidase inhibitors may be helpful in controlling postprandial blood glucose in people with Type 1 diabetes because of the drug’s ability to block the absorption of carbohydrate. Also, because of the insulin resistance that occurs in puberty, metformin has been shown to improve metabolic control in adolescents with Type 1 diabetes. This effect seems to be associated with improved insulin-induced glucose uptake by tissues. In both situations, oral medicines are not a substitute for insulin. They are used in addition to the insulin regimen. It should be noted that these are “off-label” uses of these drugs; neither is approved by the U.S. Food and Drug Administration for marketing as a treatment for Type 1 diabetes.

During pregnancy, insulin has always been the treatment of choice for diabetes because oral medicines have long been thought to increase the risk of damage to the fetus. However, research into certain oral medicines (particularly glyburide and metformin) has led to their consideration as treatment for gestational diabetes and Type 2 diabetes during pregnancy. This is an area of controversy, however, and one in which a woman and her health-care team have to carefully weigh the risks and benefits together.

Getting the most from your medicines

Caring for your diabetes requires attention to detail in many areas, from meal planning to physical activity to monitoring of blood glucose. With everything else to consider, it’s no surprise that some people occasionally forget to take their oral medicines. In fact, research shows that nearly one in three people with Type 2 diabetes who need oral medicines fail to take them daily. Unfortunately, this doubles the likelihood of hospitalizations for heart- or diabetes-related complications.

What should you do if you forget to take your diabetes pill or pills? As a general rule, you can take a missed dose of medicine as soon as you remember it. However, if it is almost time for your next scheduled dose, you may be advised to skip the missed dose and go back to your regular schedule. Do not take a double dose. Taking a missed dose of repaglinide or nateglinide between meals could result in hypoglycemia because these drugs stimulate the release of insulin from the pancreas. If you miss a dose of acarbose or miglitol, taking it between meals will have little effect, because its action is based on stopping the absorption of carbohydrate after eating. Instead, resume taking it at your next meal.

Treating diabetes is an art grounded in science. Work with your diabetes team to choose and use the oral medicine or combination of oral medicines that works best for your situation. You may want to consider the cost of the drug and the number of times per day you have to take it, as well as side effects and possible interactions with any other drugs you may take. Fortunately, today’s diabetes toolbox is well stocked with options to help you reach your blood glucose targets!

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to view Oral Diabetes Medicines at a Glance and Effectiveness of Oral Medicines

 

 

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Statements and opinions expressed on this Web site are those of the authors and not necessarily those of the publishers or advertisers. The information provided on this Web site should not be construed as medical instruction. Consult appropriate health-care professionals before taking action based on this information.

 

 

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