Diabetes and Lipid Clinic of Alaska



About Sulfonylurea Agents

Sulfonylurea agents are drugs 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 class of drugs called anti-diabetic agents that are prescribed when meal planning, weight loss and exercise alone are not effective in controlling 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 are medications that have two major effects:

  • Help the body to produce additional insulin. This hormone carries glucose out of the bloodstream and into cells.
  • 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 diet and exercise patterns may be balanced with changes to the sulfonylurea dose. 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.

Treatment with sulfonylureas is not always the best option for patients. For example, 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 treatments once their medical condition changes or is brought under control. Conditions that may dictate insulin therapy over sulfonylureas include:

  • Pregnancy
  • Diabetic coma
  • Ketoacidosis (high levels of ketones, an acid in the blood)
  • 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 anti-diabetic 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 insulin injections to control the type 2 diabetes. Sulfonylureas and most other anti-diabetic agents 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 sufonylurea agents 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

First Generation












Second Generation




Glucotrol XL


Glynase, Micronase



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 (a type of water pill). 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 ketones (an acidic waste) in the blood (diabetic ketoacidosis) or other types of acidosis (acid in the blood)
  • Diabetic coma
  • Any other condition in which insulin needs change rapidly
  • Severe burns or infection
  • High fever
  • Recurring diarrhea
  • Female hormone changes (e.g., during puberty, pregnancy, or menstruation)
  • Severe infections
  • Overactive or underactive adrenal gland or thyroid gland
  • Underactive pituitary gland
  • Problems with intestines
  • Slow stomach emptying (e.g., gastroparesis)
  • Recurring vomiting
  • 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 of weight. This can be a significant issue for many patients, because the majority of people with type 2 diabetes are also overweight or obese. Patients who gain weight may have to try another anti-diabetic agent to treat their symptoms.

There have been reports that sulfonylureas can increase the risk of death from heart and blood vessel disease. However, this has not been proved in research. In fact, there is evidence that some sulfonylureas may actually 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 the alleged risks associated with sulfonylureas, failure to reduce high glucose levels may be more likely to damage their health and cause complications.

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 with their physician. This is particularly important if they are taking medication. People taking the sulfonylurea chlorprpamide are advised not to drink alcohol because of the risk of severe hypoglycemia. For more information, see Alcohol & Diabetes.
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 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
  • Sun sensitivity
  • 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 depression or swelling (edema) or puffiness of the face, ankles or hands.

Pregnancy use issues with sulfonylurea agents

Sulfonylureas generally should not be used by pregnant women. Doctors may use glipizide during pregnancy because it does not cross the placenta. During and after pregnancy, a woman’s need for insulin fluctuates. Physicians typically 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. Women who are pregnant or thinking of becoming pregnant should inform their physician.

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 has been uncommon in children until recent years. Clinical studies into pediatric use of sulfonylureas are under way.

In November 2005, the U.S. Food and Drug Administration (FDA) approved changing the label for glimepiride to add language on pediatric use. The wording 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.

Elderly use issues with sulfonylurea agents

Side effects associated with sulfonylureas may be more pronounced in elderly patients. This is especially true if more than one anti-diabetic agent is being taken or if the patient uses other medicines that affect glucose (blood sugar). For this reason, low glucose (hypoglycemia) is more common in older adults.

Please consult with the medical professionals at Diabetes and Lipid Clinic of Alaska for further information.

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