Sulfonylurea Agents

Sulfonylurea Agents

Also called: Sulfonylureas


Sulfonylurea agents are medications that can be used, along with exercise and diet, to lower glucose (blood sugar) levels in patients with type 2 diabetes. These antidiabetic agents stimulate the pancreas to release more insulin, which transports glucose out of the bloodstream and into the cells to be used for energy. In addition, sulfonylureas themselves help move glucose into cells.

Sulfonylureas were introduced in the 1950s as the first class of oral diabetes medications. These drugs can be prescribed to treat type 2 diabetes when meal planning, exercise and other lifestyle changes fail to adequately lower glucose levels. Possible side effects of sulfonylureas include hypoglycemia and weight gain.

Patients who take sulfonylureas often find that the medication loses its effectiveness after five to seven years of therapy. In such cases, another antidiabetic agent may be used to replace or enhance the sulfonylurea. If all of these methods fail to lower glucose levels, insulin therapy may be prescribed.

About sulfonylurea agents

Sulfonylurea agents are drugs that can be used to treat type 2 diabetes. These medications help lower glucose (blood sugar) levels in patients, an important factor in controlling the disease and its complications. Sulfonylureas belong to a group of drugs called antidiabetic agents that are prescribed when meal planning, exercise and weight loss alone cannot control type 2 diabetes.

People with type 2 diabetes have cells that are resistant to glucose. In addition, many of these patients do not produce enough insulin to carry the glucose from the bloodstream to the cells. Sulfonylureas have two major effects:

  • They help the pancreas produce additional insulin. This hormone carries glucose out of the bloodstream and into cells.
  • They help glucose enter cells. People with type 2 diabetes have cells that are resistant to glucose.

Sulfonylureas are usually taken one to two times a day before meals. Prescriptions that are to be taken once a day usually are taken before breakfast, and twice-daily prescriptions are usually taken before breakfast and supper. However, a physician can best advise individual patients about when to take these medications.

The appropriate dose depends on the patient’s diet and exercise habits. Changes in eating and activity patterns may be balanced with changes to the sulfonylurea dosage. Patients who change any of these factors (e.g., diet, activity level, medication) are advised to perform glucose monitoring more frequently to make sure they do not drop too low (hypoglycemia) or rise too high (hyperglycemia).

Patients must continue to practice good health habits as recommended by a physician. Failure to do so may render sulfonylureas ineffective.

Researchers in 2006 reported that many patients with neonatal diabetes, a rare condition that begins in infancy and is generally treated with insulin, may benefit from sulfonylureas and might not need insulin therapy.

Treatment with sulfonylureas is not always the best option for patients. People who are prone to hypoglycemia or who have hypoglycemia unawareness (difficulty sensing low blood sugar) may be prescribed biguanides or other treatments instead. Also, patients with certain medical conditions may find insulin therapy more beneficial, especially if the condition causes fluctuations in the patient’s insulin needs. In some cases, patients will be able to return to sulfonylurea therapy once their medical condition changes or is brought under control.

Sulfonylureas and other antidiabetic agents are not used to treat diabetic ketoacidosis, a condition involving severe hyperglycemia and the buildup of an acidic waste product called ketones.

Other conditions that may dictate insulin therapy or other treatment over sulfonylureas include:

  • Pregnancy
  • Severe injury, burn or infection
  • Major surgery

After five to seven years, it is not unusual for patients to find that sulfonylureas become less effective. This may cause glucose levels to rise to unacceptable levels. Dosage levels may be adjusted, or an alternate antidiabetic agent may be tried. In some cases, combining a sulfonylurea with another medication will improve treatment results.

If these alternatives fail to lower glucose levels, the patient may require regular treatment with insulin administered by syringe injection or other means. Sulfonylureas and other diabetes pills cannot help patients who have type 1 diabetes because these patients cannot produce insulin from their pancreas. Insulin administration is necessary to help these patients control their glucose levels.

Types and differences of sulfonylurea agents

Sulfonylurea agents can be divided into two categories: first-generation and second-generation. First-generation sulfonylureas are being used less frequently, as their second-generation successors have several advantages, including:

  • Reduced side effects
  • 100 to 200 times greater potency
  • Wider range of treatment options
  • Longer acting than most first-generation pills

First Generation


                  * no longer available in the United States

Second Generation

glipizideGlucotrol, Glucotrol XL
glyburideDiaBeta, Glynase, Micronase


glipizide and metformin (a biguanide)Metaglip
glyburide and metforminGlucovance
glimepiride and rosiglitazone (a thiazolidinedione [TZD])Avandaryl
glimepiride and pioglitazone (a TZD)Duetact

Sulfonylureas may also be prescribed with other antidiabetic agents –- such as alpha-glucosidase inhibitors, DPP-4 inhibitors or injected incretin mimetics –- or with insulin.

Conditions of concern with sulfonylurea agents

Patients should inform their physician if they have had a history of allergic reactions to sulfonamide-type (sulfa) medicines or sulfonylureas. These include thiazide diuretics. Patients should also reveal allergies to other substances such as foods, preservatives or dyes.

Past or present conditions that may affect use of sulfonylureas include:

  • High levels of the acidic wastes known as ketones in the blood (ketosis, which can lead to diabetic ketoacidosis) or other types of acidosis
  • Diabetic coma
  • Any other condition in which insulin needs change rapidly
  • Severe burns or infection
  • High fever
  • Female hormone changes (e.g., during puberty, pregnancy or menstruation)
  • Overactive or underactive adrenal glands or thyroid gland, or underactive pituitary gland
  • Gastrointestinal problems such as recurring vomiting, recurring diarrhea or slow emptying of the stomach (gastroparesis),
  • Any other condition that causes severe changes in glucose (blood sugar) or low glucose (hypoglycemia)
  • Heart disease, kidney disease (e.g., diabetic nephropathy) or liver disease
  • Undernourished or weakened physical condition
  • Severe mental stress

Potential side effects and overdose symptoms

As sulfonylureas boost insulin levels, some patients may gain between 5 and 10 pounds. This can be a significant issue for many patients, because the majority of people with type 2 diabetes are already overweight or obese. Patients who gain weight may have to try another antidiabetic agent or other treatment.

Some research has linked sulfonylureas to increased risk of death from heart and blood vessel disease. However, there is also evidence that some sulfonylureas may help prevent such diseases. Experts do know that patients with diabetes are already more likely to have cardiovascular problems, especially if they do not control their glucose (blood sugar). Though patients should be aware of possible risks associated with sulfonylureas, failure to reduce high glucose levels may be more likely to damage their health and cause complications.

Recent preliminary research comparing cancer rates in people using metformin (a biguanide), sulfonylureas or insulin suggests a possible increased cancer risk in people using sulfonylureas or insulin. However, additional research is needed to establish any such connection.

Sulfonylureas may cause side effects. Immediate medical care should be sought if a patient experiences convulsions (seizures) or unconsciousness.

In some patients, sulfonylureas can cause low glucose levels(hypoglycemia). It is important that patients learn to recognize the symptoms that indicate low glucose levels. Sulfonylurea overdose can also cause hypoglycemia. Symptoms can be similar to the medication’s side effects but are usually more severe. To prevent hypoglycemia, patients are generally advised to not try to make up for missed doses unless it is within two hours of the regularly scheduled time to take the sulfonylurea.

Drinking alcohol also increases the risk of hypoglycemia. Under all circumstances, diabetes patients should discuss with their physician whether they should drink alcohol. This is particularly important if they are taking medication. People taking the sulfonylurea chlorpropamide are advised not to drink alcohol because of the risk of severe hypoglycemia, and other individuals may also be advised by their physician not to drink alcohol.

Patients who experience the following symptoms should also consult a physician:

  • Anxiety or nervousness
  • Blurred vision
  • Cold sweats or cool, pale skin
  • Confusion, slurred speech or other behavioral changes that may mimic drunkenness
  • Inability to concentrate
  • Drowsiness
  • Excessive hunger (polyphagia)
  • Rapid heartbeat
  • Headache
  • Nausea
  • Nightmares or restless sleep
  • Shakiness
  • Fatigue or weakness

Other possible symptoms that require medical attention include:

  • Skin peeling, redness, itching (pruritus), thinning or rash
  • Chest pain
  • Chills
  • Coughing up blood
  • Dark urine
  • Fever
  • Fluid-filled blisters
  • Increased sputum (phlegm)
  • Increased sweating
  • Light-colored stools
  • Sensitivity to the sun
  • Shortness of breath
  • Sore throat
  • Unusual bleeding or bruising
  • Yellow eyes or skin (jaundice)

The following possible side effects do not necessarily require medical attention and usually disappear over time:

  • Changes in sense of taste
  • Constipation or diarrhea
  • Dizziness
  • Frequent urination (polyuria)
  • Heartburn
  • Increased or decreased appetite
  • Flatulence
  • Stomach pain, fullness or discomfort
  • Vomiting
  • Difficulty in focusing the eyes

Some patients taking chlorpropamide or tolbutamide may retain excess body water. Patients should check with a physician when suffering swelling (edema) or puffiness of the face, ankles or hands.

Drug interactions with sulfonylurea agents

Patients should consult their physicians before taking any additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications. Drugs and substances that can adversely affect the performance of sulfonylurea agents or that can alter glucose (blood sugar) levels include:

  • Alcohol
  • Allergy, asthma, cold or hay fever medications
  • Certain antibiotics (chloramphenicol, fluoroquinolones)
  • Anticoagulants
  • Certain antihypertensives (thiazide diuretics, beta blockers, guanethidine
  • Aspirin or other salicylates
  • Azole antifungals, used to treat yeast infections and other fungal infections
  • Corticosteroids, an anti-inflammatory class of immunosuppressives
  • Monoamine oxidase inhibitors (MAOIs), a class of antidepressants, and possibly other antidepressants
  • Asparaginase (used to treat leukemia or other cancer)
  • Lithium (medication for bipolar disorder)
  • Octreotide (diarrhea medication)
  • Pentamidine (pneumonia medication)
  • Quinidine (heart rhythm drug)
  • Quinine (malaria drug)
  • Ranitidine (drug for ulcers and gastroesophageal reflux disease, GERD)

Pregnancy use issues with sulfonylurea agents

Sulfonylureas are generally not used during and shortly after pregnancy, when a woman’s need for insulin fluctuates. Physicians may recommend injections of insulin to address these fluctuating needs and control glucose (blood sugar).

Pregnant women must maintain the near-normal glucose levels, as hyperglycemia can cause birth defects or excessive weight gain in babies. Patients who are pregnant or thinking of becoming pregnant should inform their physician.

Pregnant women who do use sulfonylureas are typically advised to stop using them at least two weeks before the delivery date (or one month before delivery if taking chlorpropamide and glipizide).

Some sulfonylureas, including chlorpropamide and tolbutamide, have been shown to pass into human breast milk. In addition, glimepiride passes into the milk of rats. It is not known whether or not other sulfonylureas pass into breast milk. Nursing mothers should consult with a physician before taking sulfonylureas.

Child use issues with sulfonylurea agents

Type 2 diabetes was rare in children until recent years. Metformin, a biguanide, was the only antidiabetic agent cleared for children until the U.S. Food and Drug Administration (FDA) in 2005 approved changing the label for glimepiride to add language on pediatric use. The FDA noted a study finding that adverse reactions in children treated with the drug were similar to those experienced by adults. Four percent of the diabetic children treated with glimepiride experienced hypoglycemia, compared to 1 percent of children treated with metformin.

Other clinical studies into pediatric use of sulfonylureas are under way.

Elderly use issues with sulfonylurea agents

Side effects associated with sulfonylureas, including hypoglycemia, may be more pronounced in elderly patients. This is especially true if more than one antidiabetic agent is being taken or if the patient uses other medicines that affect glucose (blood sugar).

Questions for your doctor about sulfonylureas

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions and treatments. Patients may wish to ask their doctor the following questions about sulfonylurea agents:

  1. Do you recommend sulfonylureas to treat my type 2 diabetes?

  2. Which sulfonylurea will I use?

  3. What is my dosage and frequency?

  4. How and when should I take the drug?

  5. What should I do if I forget a dose or take an extra dose?

  6. What side effects might I experience? Is hypoglycemia a concern for me? Am I likely to gain weight?

  7. What should I do if I experience symptoms of hypoglycemia?

  8. At what point should I inform you of side effects?

  9. What should I do if I develop ketosis or diabetic ketoacidosis?

  10. Do any of my other conditions or medications rule out sulfonylureas?

  11. What other treatments might be used if I have difficulty tolerating sulfonylureas?

  12. For how many years is this drug likely to be effective for me? What will be done if this drug begins to be less effective in controlling my glucose?

  13. Can exercise and diet reduce my need for sulfonylureas? If so, how will this be monitored and adjusted?

  14. Can sulfonylureas be safely used by pregnant women, nursing women, children or elders?

  15. If my baby has diabetes or my diabetes began in infancy, could this be treated with a sulfonylurea instead of insulin?
Scroll to Top