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Oral Diabetes Prescription Medications

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What are oral diabetes medications and how do they work?

Insulin is a hormone produced by cells in the pancreas called beta cells. Insulin helps the body use blood glucose (a type of sugar) for energy. People with type 2 diabetes do not make enough insulin and/or their bodies do not respond well to it, leading to elevated blood sugar levels. Oral diabetes medications bring blood sugar levels into the normal range through a variety of ways.

For what conditions are diabetes pills used?

Oral diabetes medications are only used to treat type 2 or non-insulin-dependent diabetes. Patients with type 1 diabetes are dependent on insulin for their treatment.

Are there differences among types of oral diabetes medications?

Medications that increase insulin production

The earliest oral diabetes drugs were the sulfonylureas. These work by stimulating the pancreas to produce more insulin. The oldest of these drugs still on the market is chlorpropamide (Diabinese), which has been used for more than 50 years. The second-generation sulfonylureas are taken once or twice a day. They include glipizide (Glucotrol, Glucotrol XL), glyburide (Micronase, DiaBeta, Glynase), and glimepiride (Amaryl).

Meglitinides also stimulate the release of more insulin from beta cells. Repaglinide (Prandin) and nateglinide (Starlix) are taken before each of three meals.

Medications that decrease glucose production and increase insulin sensitivity

One drug makes up the class of oral diabetes medications known as the biguanides, and that is metformin (Glucophage). It works by decreasing production of glucose by the liver and by making muscle more sensitive to insulin. The thiazolidinediones, rosiglitazone (Avandia) and pioglitazone (Actos), work in a similar way.

Medications that slow the breakdown of carbohydrates

Alpha-glucosidase inhibitors approach the blood glucose issue in a different way. By inhibiting the breakdown of starches in the intestine, these medications slow the rise in blood sugar normally seen after a meal. Examples include acarbose (Precose) and meglitol (Glyset).

Medications that increase insulin production and decrease glucose production

In the last category of oral diabetes medications is the DPP-4 inhibitor sitagliptin (Januvia). This drug works by inhibiting the action of an enzyme in the body that leads to increase in insulin release. It also decreases the production of glucose by the liver.

What non-insulin injectable drugs are approved for diabetes?

During digestion, pancreatic beta cells release not only insulin, but in a much smaller amount, the hormone amylin, which helps mediate sharp rises in blood glucose levels following meals. Pramlintide (Symlin) is a new, synthetic form of amylin that may help improve blood glucose control for some type 1 and type 2 diabetic people who use insulin. Pramlintide has few side effects (nausea is the main one) but it adds another set of injections to a diabetic person's daily pharmaceutical routine, as it cannot be mixed in the same syringe with insulin.

Another non-insulin injection for people with diabetes is exenatide (Byetta). This medication, originally derived from a compound found in the saliva of the Gila monster, triggers insulin release from the pancreas when blood glucose levels rise. Exenatide is meant to be used along with oral diabetes drugs. It is dosed twice daily and should be injected within an hour of the morning and evening meals. Recently, the FDA warned that exenatide may increase the risk of severe even fatal pancreatitis (inflammation of the pancreas) and that the drug should be discontinued and not restarted if signs and symptoms of pancreatitis develop (severe abdominal pain, for example). It is not for use in people with type 1 diabetes.

What are the side effects of the non-insulin diabetes medications?

Many people with type 2 diabetes will take a combination of medications to help control their diabetes. With combination therapy, there is increased risk for low blood sugar.

The sulfonylureas may cause hypoglycemia (low blood sugar), skin rash or itching, sensitivity to sunlight, upset stomach, and weight gain.

The meglitinides may cause hypoglycemia and weight gain.

People taking biguanides may develop lactic acidosis, a rare but severe side effect. Excessive alcohol intake while on metformin can contribute to development of lactic acidosis. Other side effects include metallic taste in the mouth and diarrhea.

Thiazolidenediones can increase risk of heart failure and should not be used in patients with symptoms of heart failure. Liver enzymes should be checked regularly with use. Other side effects include weight gain, fatigue, swelling of the legs or ankles, increased risk for fractures in female patients. Avandia may have a potential increased risk for heart attack.

Alpha-glucosidase inhibitors may cause gastrointestinal problems (nausea, gas, bloating), although they are usually fleeting.

The DPP-4 inhibitor sitagliptin (Januvia) may cause serious allergic reactions, sore throat, upper respiratory infection, and headache.

Pramlintide (with insulin) may cause gastrointestinal problems (nausea, vomiting, abdominal pain, anorexia), slight weight loss, headache, fatigue, dizziness, coughing, sore throat, and skin reactions at the injection site.

Side effects of exenatide may include slight weight loss, nausea, vomiting, and diarrhea.

What are the drug interactions with non-insulin diabetes medications?

Many drugs can affect your blood sugar levels, affecting in turn how well your diabetes medication works. Make sure your doctor is aware of all other medications and supplements you are taking to ensure the proper dosing of your diabetes medication.

There is much overlap of medications that may interact with oral diabetes drugs. These include but are not limited to some:

Digestive enzyme medications (such as amylase, pancreatin) may reduce the effectiveness of alpha-glucosidase inhibitors and should not be taken at the same time.

Pramlintide

These drugs can cause potentially severe hypoglycemia when used with insulin and can delay absorption of some oral drugs given at the same time. They should not be used with other drugs affecting gastrointestinal motility or agents that work by affecting gut absorption of nutrients (such as alpha-glucosidase inhibitors).

Exenatide (Byetta)

Because Byetta may affect absorption of some drugs given orally, including antibiotics, those drugs should not be used within an hour of a Byetta injection. The drug may also interact with warfarin.

What are the warnings and precautions for non-insulin diabetes medications?

Diabetes medications can have interactions with other medications or supplements being used. Use of more than one diabetes medication can increase the risk for hypoglycemia. Beta-blocker medications can mask the symptoms of hypoglycemia.

Sulfonylureasmay increase the risk of death from cardiovascular disease. Prolonged exercise and alcohol intake increase the risk for hypoglycemia. Patients undergoing surgery or who have had recent trauma, stress, or infection may need to switch from a sulfonylurea to insulin to manage blood sugar levels. People with kidney or liver disease need to take precaution.

Because meglitinides may cause hypoglycemia, they should be taken right before meals to minimize the possibility of hypoglycemia. If a meal is to be skipped, the dose of the medication should also be skipped.

Thiazolidinediones may cause or exacerbate heart failure. Trouble breathing, rapid weight gain and fluid retention may indicate the onset of heart failure.

Avandia may potentially increase the risk of heart attack.

Alpha-glucosidase inhibitors should not be used in people with intestinal diseases such as inflammatory bowel disease or intestinal obstruction. People with kidney dysfunction may not be able to these medications.

Alpha-glucosidase inhibitors should be taken with the first bite of each meal.

Patients with kidney disease may require dosage adjustment if they are using a DPP-4 inhibitor.

People with a history of liver disease, heavy drinking, or kidney disease may not be able to take biguanides. Inform medical personnel of biguanide use prior to any radiological tests which require injection of dye.

Severe hypersensitivity reactions have occurred during use of sitagliptin.

Pramlintide is only appropriate for certain people with diabetes who use insulin and are having problems maintaining their blood sugar levels. Because of the potential for severe hypoglycemia with the use of pramlintide is with insulin, adjustments to insulin dosage and more frequent glucose monitoring may be necessary. Insulin and pramlintide should not be mixed in the same syringe.

Exenatide may increase the risk of severe even fatal pancreatitis. Byetta should not be used in people with type 1 diabetes or to treat diabetic ketoacidosis.

Patients with severe kidney disease or gastrointestinal disease should not use exenatide.

Hypersensitivity reactions may occur following treatment with exenatide due to formation of antibodies.

What are some examples of oral medications used for diabetes?

Sulfonylureas

  • Chlorpropamide (Diabinese)
  • Glyburide (Micronase, Diabeta, Glynase PresTab)
  • Glipizide (Glucotrol, Glucotrol XL)
  • Glimepiride (Amaryl)
  • Tolbutamide
  • Acetohexamide
  • Tolazamide (Tolinase)

Meglitinides

  • Nateglinide (Starlix)
  • Repaglinide (Prandin)

Thiazolidinediones

  • Rosiglitazone (Avandia)
  • Pioglitazone (Actos)

Biguanides

Alpha-Glucosidase Inhibitors

  • Acarbose (Precose)
  • Meglitol (Glyset)

DPP-4 Inhibitor

  • Sitagliptin (Januvia)

Oral diabetes medications may also come in combination tablets such as Metaglip (glipizide/metformin), Prandimet (repaglinide/metformin), Glucovance (glyburide/metformin), Janumet (sitagliptin/metformin), Avandamet (rosiglitazone/metformin), Avandaryl (rosiglitazone/ glimepiride), Duetact (pioglitazone/glimepiride), Actoplus Met (pioglitazone/metformin).

SOURCES:
American Diabetes Association www.diabetes.org
Food and Drug Administration www.fda.gov
Wikipedia www.wikipedia.org
WebMD www.webmd.com
www.diabetes.niddk.nih.gov
National Institute of Diabetes, Digestive and Kidney Diseases
FDA Drug Database www.accessdata.fda.gov
Daily Med www.dailymed.nlm.nih

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