WHATEVER YOUR PRACTICE setting, you probably care for someone with diabetes-and odds are, he has Type 2 diabetes. More common than Type 1 diabetes, which develops when the pancreas can't produce any insulin, Type 2 diabetes occurs when the pancreas produces an insufficient amount or the body's ability to use insulin is impaired. (Review the pathophysiology in A Vicious Cycle: Hyperglycemia and Hyperinsulinemia.)

Keeping glucose levels near normal helps prevent long-term complications and improves quality of life for people with diabetes. Some with Type 2 diabetes achieve this goal with meal planning and exercise alone, but most rely on medications as well.

At various stages of their disease, most people with Type 2 diabetes need different drug types and combinations. Here, we'll review available oral medications and explain what's unique about each type. (To learn about insulin therapy, see "Diabetes Update, part 2: Unlock the Mysteries of Insulin Therapy" later in this issue.)

A touch of class

Five classes of oral medications are used to treat Type 2 diabetes, each having a different mechanism of action (see Using Oral Medications to Treat Type 2 Diabetes). Your patient's physiologic characteristics, the drug's site of action, and his response to therapy all play a role in determining what's appropriate for him: an oral drug alone, a combination of oral drugs, an oral drug with insulin, or insulin alone.

Make sure your patient understands the progression of therapy, including the possibility that he'll need to use insulin in the future. Explain that because pancreatic function declines over time, the number and type of medications he takes will change or increase.

Therapy choices will be based on his blood glucose and hemoglobin A1C levels. Fasting and postprandial blood glucose measurements indicate his levels throughout each day. The A1C level reveals the big picture of glucose control over the previous 8 to 12 weeks, with the previous 2 weeks most heavily weighted. These are the recommended targets:

* fasting blood glucose, 90 to 130 mg/dl

* postprandial blood glucose, less than 180 mg/dl

* A1C, less than 7%.

Reviewing the choices

Five classes of oral drugs-sulfonylureas, meglitinides, biguanide, alpha-glucosidase inhibitors, and thiazolidinediones-are available for patients whose insulin production or utilization is inadequate due to Type 2 diabetes.

Sulfonylureas. The oldest class of oral diabetes drugs, these insulin "secretagogues" primarily stimulate the pancreas to release insulin, particularly in the early course of Type 2 diabetes. First-generation sulfonylureas-tolbutamide, chlorpropamide, and tolazamide-are rarely prescribed today because they depend on renal excretion and tax the kidneys. Second-generation glyburide, glipizide, and glimepiride are more potent and don't require renal excretion. Except for chlorpropamide, which is excreted partially unchanged in the urine, sulfonylureas are metabolized in the liver.

An average-weight adult without lipid abnormalities is an ideal candidate for sulfonylurea therapy early in the course of Type 2 diabetes. Therapy starts with low, single daily doses; the dosage is gradually increased until the patient reaches his target glucose level.

If your patient doesn't reach his target using maximum doses of sulfonylureas, exceeding the recommended dosage won't help. About 20% of people who take sulfonylureas don't respond to therapy at all (primary failure). Another 10% respond well at first, but their glucose control diminishes over time (secondary failure).

Meglitinides. Another class of insulin secretagogues, meglitinides have many of the same actions and adverse effects as sulfonylureas. Like the sulfonylureas, they increase insulin release to treat postprandial hyperglycemia, but they act more rapidly.

The two available meglitinides are repaglinide (Prandin) and nateglinide (Starlix). Their effects, which are glucose-dependent, decrease when the patients blood glucose level decreases. They work well in the elderly and in patients with renal impairment. Because they're metabolized in the liver, use them cautiously in anyone with moderate to severe liver impairment.

Biguanide. Currently, metformin (Glucophage) is the only biguanide on the market. It works primarily by reducing hepatic glucose production and lowers fasting blood glucose levels. It also enhances tissue response to insulin and improves glucose transport into the cells. Used alone, it doesn't cause hypoglycemia because it doesn't stimulate insulin secretion.

Metformin is primarily excreted through the kidneys, so document your patients baseline serum creatinine level before he starts therapy. If his renal function is impaired, the drug could accumulate in his bloodstream and cause lactic acidosis. Baseline liver function tests are recommended too because lactate metabolism occurs in the liver.

Metformin typically doesn't promote weight gain and may help improve blood lipid levels, so it's a good choice for an obese patient or someone with lipid abnormalities. The dosage is typically started low and gradually increased until the patient's blood glucose and A1C values reach target levels.

Metformin should be discontinued and another drug ordered if your patient develops cardiovascular collapse, acute myocardial infarction, or an acute episode of heart failure; if he has major surgery; or if he's at risk for acute renal dysfunction or tissue hypoperfusion.

Alpha-glucosidase inhibitors. This drug class includes acarbose (Precose) and miglitol (Glyset). Metabolized by intestinal bacteria and digestive enzymes, alpha-glucosidase inhibitors delay carbohydrate absorption from the small intestine. They're most appropriate for someone with normal fasting blood glucose levels and significantly elevated postprandial readings because they don't directly affect fasting levels. The best way to gauge effectiveness of therapy with acarbose or miglitol is to monitor the patient's 2-hour postprandial blood glucose levels.

These drugs don't pose a risk of hypoglycemia unless given in combination with a sulfonylurea, meglitinide, or insulin. In that case, the patient must take special precautions to treat hypoglycemia because alphaglucosidase inhibitors prevent absorption of sucrose (table sugar). Only a carbohydrate source that contains glucose or lactose (such as glucose tablets or milk) will effectively raise his blood glucose level.

Thiazolidinediones. The two currently available thiazolidinediones, rosiglitazone (Avandia) and pioglitazone (Actos), combat Type 2 diabetes by increasing insulin sensitivity at insulin receptor sites on the cells. They're most appropriate for adults whose bodies produce insulin but can't use it because of inadequate or ineffective insulin receptor sites. These drugs don't cause hypoglycemia and may have positive effects on lipid levels and blood pressure.

Thiazolidinediones are primarily metabolized in the liver, so the patient should undergo liver function testing before starting therapy. During therapy, he should follow the drug manufacturer's recommendations for further testing.

Combination therapy. Once an oral drug becomes ineffective, simply substituting another rarely works. But combination therapy can be highly effective. For example, oral drugs from two or more classes may be combined, or an oral drug may be combined with a bedtime dose of NPH or glargine insulin. Metformin or insulin is a common choice for combination therapy with sulfonylureas.

Formulations that combine two classes of oral drugs are now available and may help patients take their medications more easily. The contraindications and potential adverse reactions for oral combinations are the same as for individual drugs. Three types are currently available in different strengths: glyburide and metformin (Glucovance), glipizide and metformin (Metaglip), and rosiglitazone and metformin (Avandamet).

If your patient is starting a new combination of diabetes drugs, teach him all the implications. For example, if he's been taking metformin alone, he may not know about the risk of drug-induced hypoglycemia that could occur when insulin, a sulfonylurea, or a meglitinide is added to his regimen. Teach him how to prevent, recognize, and treat hypoglycemia.

Talking the talk

When you talk with your patient about oral medications for Type 2 diabetes, emphasize that they aren't an oral form of insulin. Explain that he'll probably take different drugs or combinations and that a change in his drug regimen doesn't mean his condition has worsened. It simply means that other medications can better help maintain his blood glucose levels.

Besides general information, teach your patient these key points:

* the name, type, class, and dose of each prescribed medication

* what to do if he forgets or skips a dose

* potential adverse responses

* timing in relation to meals

* the need to titrate his doses based on his responses

* the importance of taking all his currently prescribed medications because each one acts differently in his body

* the importance of continued meal planning and exercise to help manage his blood glucose levels

* when he should notify the health care provider (for example, if he has two or more hypoglycemic reactions in a week or his blood glucose level exceeds 240 mg/dl 2 days in a row).

Treating Type 2 diabetes is becoming more complex and costly as more medications and combination therapies become available. Carefully assess your patient's willingness and ability to buy his prescribed drugs and use them appropriately.

He needs to learn self-blood glucose monitoring too. Health care insurers are becoming increasingly willing to pay for monitoring supplies. Teach your patient how to use his blood glucose meter and alter his food intake, activity, and medication based on the results.

Finally, offer information about programs or support groups for people with diabetes in his community.

Staying abreast of change

The number of oral medications used to combat Type 2 diabetes keeps growing. By staying abreast of the options, you can help your patient understand and take charge of his disease.

SELECTED WEB SITES

American Association of Diabetes Educators: http://www.aadenet.org

National Diabetes Education Program: http://ndep.nih.gov

Last accessed on February 3, 2004.

SELECTED REFERENCES

American Diabetes Association: "Standards of Medical Care for Patients with Diabetes Mellitus," Diabetes Care. 26(Suppl., 1):S33-S50, January 2003.

Buse, J.: "Progressive Use of Medical Therapies in Type 2 Diabetes," Diabetes Spectrum. 13(4):211-220, October 2000.

McCulloch, D.: "Comprehensive Management of Type 2 Diabetes," Hospiial Practice. 35(9):33-48, September 15, 2000.

Riddle, M.: "Managing Type 2 Diabetes over Time: Lessons from the UKPDS," Diabetes Spectrum. 13(4):194-196, October 2000.

White, J., et al: "Pharmacologic Therapies," in A Core Curriculum for Diabetes Education, 5th edition, M. Franz (ed). Chicago, Ill., The American Association of Diabetes Educators, 2003.

BY MARTHA MITCHELL FUNNELL, RN, CDE, MS, AND DIANA L. BARLAGE, RN, CDE

Martha Mitchell Funnell is director for administration at Michigan Diabetes Research and Training Center, and Diana L. Barlage is a clinical nurse at the University of Michigan Health System, both in Ann Arbor.

Ms. Funnell has disclosed financial affiliations with Aventis Pharmaceulicals, Inlight Communications, Novo Nordisk, Takeda Pharmaceuticals, Hypertension Diagnostics, Inc., and Pfizer.

This article has been updated from "Saying a Mouthful about Oral Diabetes Drugs" in the November issue of Nursing2000.

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