What is the difference between metformin (Glucophage) vs. glipizide (Glucotrol)?

  • Metformin and glipizide are oral medications that lower blood glucose and are used for treating type 2 diabetes.
  • Metformin is also used to treat polycystic ovaries and weight gain due to medications used for treating psychoses.
  • Brand names of metformin include Glumetza, Glucophage, and Fortamet. Brand names of glipizide include Glucotrol and Glucotrol XL.
  • Side effects of metformin and glipizide that are similar include nausea, vomiting, diarrhea, and gas.
  • Side effects of metformin that are different from glipizide include bloating and loss of appetite.
  • Side effects of glipizide that are different from metformin include headache, dizziness, heartburn, and skin rashes (which cause itching, hives, or a diffuse measles-like rash).

What is metformin? What is glipizide?

Metformin is an oral medication that lowers blood glucose (sugar) by influencing the body’s sensitivity to insulin and is used for treating type 2 diabetes. Metformin acts by increasing the sensitivity of liver, muscle, fat, and other tissues to the uptake and effects of insulin, which lowers the level of sugar in the blood. Metformin does not increase the concentration of insulin in the blood and does not cause excessively low blood glucose levels (hypoglycemia) when used alone. Metformin can reduce complications of diabetes such as heart disease, blindness, and kidney disease. Metformin is also used to treat polycystic ovaries and weight gain due to medications used for treating psychoses.

Glipizide is an oral drug used to treat type 2 diabetes. It belongs to the sulfonylurea drug class, which also includes glimepiride (Amaryl), glyburide (Diabeta, Glynase), tolbutamide, and tolazamide. Insulin is a hormone made in the pancreas that when released into the blood causes cells in the body to remove glucose (sugar) from the blood and reduces the formation of glucose by the liver. In patients with type 2 diabetes the cells in their bodies are resistant to the glucose-removing effect of the insulin, and the liver produces too much glucose, resulting in high blood sugar levels. In addition, in type 2 diabetes the pancreas is unable to produce the increased amounts of insulin necessary to overcome the resistance. Glipizide reduces blood glucose by stimulating the pancreas to produce more insulin.

What are the side effects of metformin and glipizide?

The most common side effects with metformin are

  • nausea,
  • vomiting,
  • gas,
  • bloating,
  • diarrhea and
  • loss of appetite.

These symptoms occur in one out of every three patients. These side effects may be severe enough to cause therapy to be discontinued in one out of every 20 patients. These side effects are related to the dose of the medication and may decrease if the dose is reduced.
Metformin may also cause:

  • weakness or lack of energy
  • respiratory tract infections,
  • low levels of vitamin B-12,
  • low blood glucose (hyperglycemia)
  • constipation,
  • indigestion, muscle pain,
  • heartburn, and
  • chills.

A serious but rare side effect of metformin is lactic acidosis. Lactic acidosis occurs in one out of every 30,000 patients and is fatal in 50% of cases. The symptoms of lactic acidosis are

  • weakness,
  • trouble breathing,
  • abnormal heartbeats,
  • unusual muscle pain,
  • stomach discomfort,
  • light-headedness, and
  • feeling cold.

Patients at risk for lactic acidosis include those with reduced function of the

  • kidneys or liver,
  • congestive heart failure,
  • severe acute illnesses, and
  • dehydration.

Side effects include:

  • headache,
  • dizziness,
  • nausea,
  • vomiting,
  • diarrhea,
  • heartburn, and
  • gas.

Skin rashes can occur and cause itching, hives, or a diffuse measles-like rash.
Rare but serious side effects include:

  • hepatitis,
  • jaundice, and
  • a low blood sodium concentration (hyponatremia).

Glipizide also may cause hypoglycemia. The risk of hypoglycemia increases when glipizide is combined with other glucose reducing agents.

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What is the dosage of metformin vs. glipizide?


  • For treating type 2 diabetes in adults, metformin (immediate release) usually is begun at a dose of 500 mg twice a day or 850 mg once daily. The dose is gradually increased by 500 mg weekly or 850 mg every two weeks as tolerated and based on the response of the levels of glucose in the blood. The maximum daily dose is 2550 mg given in three divided doses.
  • If extended tablets are used, the starting dose is 500 mg or 1000 mg daily with the evening meal. The dose can be increased by 500 mg weekly up to a maximum dose of 2000 mg except for Fortamet (2500 mg of Fortamet, once daily or in two divided doses). Glumetza tablets (500 -1000mg formulations are given once daily (either 1000 to 2000mg). Fortamet and Glumetza are modified release formulations of metformin. Metformin should be taken with meals.
  • For pediatric patients 10-16 years of age, the starting dose is 500 mg twice a day. The dose can be increased by 500 mg weekly up to a maximum dose of 2000 mg in divided doses.
  • Children older than 17 years of age may receive 500 mg of extended release tablets daily up to a maximum dose of 2000 mg daily. Extended release tablets are not approved for children younger than 17 years of age.
  • Metformin-containing drugs may be safely used in patients with mild to moderate renal impairment. Renal function should be assessed before starting treatment and at least yearly.
  • Metformin should not be used by patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m2 and starting metformin in patients with an eGFR between 30-45 mL/minute/1.73 m2 is not recommended.
  • Metformin should be stopped at the time of or before administering iodinated contrast in patients with an eGFR between 30 and 60 mL/minute/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Kidney function should be evaluated 48 hours after receiving contrast and metformin may be restarted if kidney function is stable.


  • The usual starting dose when using immediate release tablets is 5 mg daily administered 30 minutes before a meal.
  • The maximum dose is 40 mg daily.
  • Doses higher than 15 mg per day should be divided and given in divided doses daily.
  • The starting dose when using extended-release tablets is 5 mg daily up to a maximum dose of 20 mg daily.
  • Patients using immediate release tablets may be converted to the nearest equivalent extended-release dose.

What drugs interact with metformin and glipizide?


  • 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.
  • Ioversol (Optiray) and other iodinated contrast media may reduce kidney function, which reduces elimination of metformin, leading to increased concentrations of metformin in the blood. Metformin should be stopped 48 hours before and after use of contrast media.
  • Thiazide diuretics, steroids, estrogens, and oral contraceptives may increase blood glucose and reduce the effect of metformin. When these drugs are stopped, patients should be closely observed for signs of low blood glucose.
  • Alcohol consumption increases the effect of metformin on lactate production, increasing the risk of lactic acidosis.
  • Glipizide
  • Alcohol may prolong the action of glipizide by delaying the absorption and elimination of glipizide. Patients taking glipizide should keep alcohol consumption to a minimum.
  • Cholestyramine (Questran, Questran Light) may reduce both the absorption and effects of glipizide. Glipizide should therefore be administered 1-2 hours before cholestyramine is given.
  • Fluconazole (Diflucan) also can increase the absorption and effects of glipizide.
  • Many drugs can potentially increase or decrease glucose levels thus increasing or decreasing the effects of glipizide. Drug interactions that cause low blood glucose (hypoglycemia) can occur with:
    • nonsteroidal anti-inflammatory drugs (for example [ibuprofen]),
    • sulfa drugs,
    • warfarin (Coumadin),
    • miconazole (Oravig),
    • fluconazole (Diflucan),
    • voriconazole (Vfend),
    • beta-blockers (for example, propranolol [Inderal, Inderal LA, Innopran XL]),
    • androgens (for example fluoxymesterone [Androxy]),
    • chloramphenicol,
    • cimetidine (Tagamet HB),
    • ranitidine (Zantac),
    • clarithromycin (Biaxin),
    • MAO Inhibitors (for example, isocarboxazid [Marplan] and phenelzine [Nardil]),
    • mifepristone (Mifeprex),
    • probenecid,
    • quinolone antibiotics, and
    • selective serotonin reuptake inhibitors (for example paroxetine [Paxil], fluoxetine [Prozac], and sertraline [Zoloft].
  • Drug interactions involving glipizide which can result in high blood glucose (hyperglycemia) can occur with:
    • thiazide diuretics (for example, hydrochlorothiazide [Microzide]),
    • loop diuretics (for example, furosemide [Lasix]),
    • corticosteroids such as prednisone and methylprednisolone (Medrol),
    • phenytoin (Dilantin),
    • colesevelam (Welchol),
    • danazol and somatropin (Genotropin).
  • Rifampin may reduce the blood levels of glipizide and this may result in higher levels of sugar in the blood.

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Are metformin and glipizide safe to use while pregnant or breastfeeding?


  • There are no adequate studies in pregnant women. Most experts agree that insulin is the best treatment for pregnant women with diabetes.
  • Metformin is excreted into breast milk and can therefore be transferred to the nursing infant. Nursing mothers should not use metformin.


  • Studies of adverse effects in animal studies indicate that glipizide crosses the placenta. It is not recommended to use glipizide for the routine management of diabetes in pregnant women. Insulin is preferred. In the event that glipizide is used during pregnancy, the manufacturer recommends that it be stopped at least 1 month before the expected date of delivery.
  • According to reports, glipizide is not found in breast milk. However, the risk of developing hypoglycemia in the nursing infant should be weighed against the potential benefit to the mother of taking glipizide and a decision should be made to discontinue the drug or to discontinue breastfeeding.

Medically Reviewed on 12/21/2018



FDA Prescribing Information