glipizide and metformin

• Glipizide/metformin is a combination antidiabetic medication that contains two commonly used glucose (sugar) lowering agents, glipizide (Glucotrol) and metformin (Glucophage). These agents work in different, yet complementary ways to improve blood glucose control in patients with type 2 diabetes.
  • Glipizide is a second generation oral sulfonylurea that lowers blood glucose by stimulating the production of insulin from the pancreas. It is the major hormone responsible for regulating blood sugar.
  • Metformin is an oral biguanide antidiabetic medication that decreases the production of glucose in the liver, decreases the absorption of glucose by the intestines, and increases response to insulin.
• In clinical studies, glipizide/metformin therapy was superior in improving fasting plasma glucose, postprandial plasma glucose (blood glucose levels after a meal), and HbA1c versus treatment with either agent alone.
• Combination glipizide and metformin was approved by the FDA in October 2002.

What brand names are available for glipizide/metformin?

• There are no brand names available for glipizide/metformin in the US.
• Metaglip is a discontinued brand name for glipizide/metformin.

Do I need a prescription for glipizide/metformin?

Yes

• Glipizide/metformin is used as an adjunct to diet and exercise to improve blood glucose control in adults with type 2 diabetes.

The most common side effects associated with glipizide/metformin treatment are:

• Dizziness
• Headache
• High blood pressure
• Muscle or joint pain
• Upper respiratory tract infection
• Urinary tract infection (UTI)

Side effects related to the stomach were most commonly reported by patients who newly started treatment with glipizide/metformin and included:

• Diarrhea
• Nausea
• Vomiting
• Stomach pain
• Decreased appetite
• Metallic taste
• Gas
• Heartburn
• Weight loss

Other less common but potentially serious side effects include:

• Hypoglycemia
• Blood disorders
• Liver disease
• Kidney disease
• Rash
• Photosensitivity (sun sensitivity)
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Ovulation induction
• Low sodium levels (hyponatremia)
• Hives
• Disulfiram-like reactions (for example, heart palpitations, nausea, vomiting, dizziness, and headache)
• Reduced number of platelets
• Reduced number of white blood cells
• Anemia
• Hypersensitivity type reactions

Metformin can cause a rare but serious condition known as lactic acidosis, a build-up of acid in the blood. Lactic acidosis can cause death and requires immediate treatment.

Symptoms of lactic acidosis include:

• Tiredness
• Weakness
• Unusual muscle pain
• Pain in the stomach
• Difficulty breathing
• Dizziness
• Slow or irregular heartbeat

Patients suspected of presenting with signs or symptoms of lactic acidosis must seek emergency medical help.

• For patients inadequately controlled on diet and exercise alone: Generally, the recommended starting dose of glipizide/metformin is 2.5/250 mg administered once or twice daily. A starting dose of 2.5/500 mg twice daily may be considered for patients with fasting plasma glucose (FPG) of 280-320 mg/dL. If necessary, dosage may be increased by 1 tablet daily every 2 weeks to achieve adequate blood glucose control. The maximum daily dose is 20/2000 mg. Avoid starting treatment with the 5/500 mg strength due to the risk of hypoglycemia (low blood glucose levels).
• For patients inadequately controlled on glipizide or metformin monotherapy: Treatment may be started with either 2.5/500 mg or 5/500 mg administered by mouth twice daily with meals. To avoid hypoglycemia, the starting dose must not exceed the current dose of glipizide or metformin that the patient has been already taking.
• For patients who are already taking a combination of sulfonylurea/metformin who desire to switch to a combination pill: To avoid hypoglycemia, avoid exceeding the current dose of sulfonylurea and metformin. If necessary, the dose may be increased gradually to the minimum dosage required to achieve adequate blood glucose control.
• Patients with liver disease: Use of glipizide/metformin in patients with liver disease is generally not recommended. Liver disease increases the risk of metformin associated lactic acidosis, a rare but potentially fatal condition which causes an accumulation of acid in the body.
• Patients with kidney disease: Metformin should not be used in females with serum creatinine concentration > 1.4 mg/dL or in males with serum creatinine concentration > 1.5 mg/dL.
• Pediatrics: The safety and efficacy of glipizide/metformin has not been established in pediatric patients. Therefore, use of glipizide/metformin in this patient population is not recommended.

• Drugs which cause blood glucose levels to increase may diminish the effectiveness of glipizide/metformin therapy. These drugs include:
  • Thiazides and other diuretics
  • Corticosteroids
  • Phenothiazines
  • Thyroid medications
  • Estrogens
  • Birth control pills
  • Phenytoin (Dilantin)
  • Nicotinic acid
  • Sympathomimetics
  • Calcium channel blockers (CCBs)
  • Isoniazid (Nydrazid)
• Cimetidine (Tagamet), by decreasing the elimination of metformin from the body, can increase the amount of metformin in the blood by 40%. This may increase the frequency of side effects from metformin.
• Alcohol consumption increases the effect of metformin on lactate production, increasing the risk of lactic acidosis.
• Due to the risk of lactic acidosis, metformin containing products must be temporarily discontinued prior to the administration of radiopaque contrast dyes.
• Metformin should be held for at least 48 hours after contrast dye administration and should not be restarted until patient's kidney function returns back to normal.
• Beta blockers may increase the blood glucose lowering actions of sulfonylureas. Cardio-selective beta blockers such as acebutolol (Sectral), atenolol (Tenormin), metoprolol (Lopressor or Toprol XL), and penbutolol (Levatol) may be safer than their nonselective counterparts.
• Colesevelam (Welchol) may reduce blood levels of glipizide. Patients are advised to take glipizide 1 hour before or 4 hours after colesevelam administration to minimize the risk of their interaction.
• Concomitant use of systemic antifungals such as fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), miconazole, and voriconazole (VFEND) with glipizide may cause hypoglycemia.

• Glipizide/metformin has not been adequately evaluated in pregnant women. Due to the lack of conclusive safety data, glipizide/metformin should be avoided during pregnancy if possible. Glipizide/metformin is classified as FDA pregnancy risk category C (animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks).
• It is not known if glipizide/metformin is excreted in breast milk. Due to the lack of safety data and the potential risk for hypoglycemia in the nursing infant, use of glipizide/metformin during breastfeeding is not recommended.

What preparations of glipizide/metformin are available?

• Oral tablets (glipizide/metformin): 2.5/250, 2.5/500 or 5/500 mg

How should I keep glipizide/metformin stored?

• Tablets should be stored at room temperature between 15 C and 30 C (59 F and 86 F).