What to Know About Glucophage (Metformin)

Glucophage is one brand of metformin hydrochloride, a drug that may be prescribed to help manage blood sugar levels if you have type 2 diabetes. Metformin is an antihyperglycemic agent that helps lower production and absorption of glucose, as well as reduce insulin resistance. It is typically used as an adjunct to diet and exercise to help manage diabetes.

Glucophage belongs to a class of drugs called biguanides, which are derived from the French lilac flower. The drug comes in immediate-release or extended-release oral tablets (Glucophage XR); other extended-release metformin brands include Fortamet and Glumetza. Metformin is also available as a generic. Riomet, another form of metformin, delivers the drug in an oral solution that you drink.

Uses

According to the American Diabetes Association's (ADA) Standards of Medical Care in Diabetes, metformin, if tolerated, is the preferred initial oral diabetes medication for type 2 diabetes because it is considered safe and effective, and it may reduce cardiovascular risks.

Metformin is approved for adults and children ages 10 and over. The extended-release formula is approved for use in those 18 and over.

Unlike people with type 1 diabetes, people with type 2 still produce insulin (although production may decrease as the disease progresses). The problem is that they are either not making enough of the hormone or what they do make isn't being used efficiently.

This results in insulin resistance—the hormone is unable to direct sugar from the bloodstream to the cells for energy—and the liver and pancreas generate more insulin, even though it's not needed. The body winds up in chaos, with both high blood sugars and high insulin levels.

Glucophage helps restore normalcy by managing blood sugar in three ways:

• Lowers the liver's production of glucose
• Reduces intestinal absorption of glucose from foods
• Makes your body more sensitive to insulin by increasing glucose uptake and utilization in peripheral tissues

Research shows that, as first-line therapy for type 2 diabetes, metformin has beneficial effects on A1C (a measure of average blood glucose), weight, and cardiovascular mortality compared to sulfonylureas.

Glucophage may be used with insulin or other diabetes medications for those with type 2 diabetes.

Combination medications that contain metformin, which may be recommended instead of Glucophage if you need to take more than one drug, include:

• Actoplus Met and Actoplus Met XR (metformin + pioglitazone)
• Glucovance (metformin + glyburide)
• Invokamet and Invokamet XR (metformin + canagliflozin)
• Janumet and Janumet XR (metformin + sitagliptin)
• Jentadueto and Jentadueto XR (metformin + linagliptin)
• Kazano (metformin + alogliptin)
• Kombiglyze XR (metformin + saxagliptin)
• Metaglip (metformin + glipizide)
• Synjardy and Synjardy XR (metformin + empagliflozin)
• Xigduo XR (metformin + dapagliflozin)

Off-Label Uses

In addition to being used for diabetes, Glucophage is sometimes used off-label in polycystic ovary syndrome (PCOS) as an aid for infertility, as a weight-loss adjunct, to treat gestational diabetes, or in HIV lipodystrophy syndrome.

Studies have also found that metformin targets many pathways in the growth of cancer, and research is evaluating the possible increased survival of those with cancers such as lung cancer, breast cancer, and bladder cancer who have been treated with metformin.

Metformin is also being studied for its effect on the thyroid as it appears to reduce the risk of goiter, thyroid nodules, and thyroid cancer.

Before Taking

To assess if you're a good candidate for Glucophage or another form of metformin, your healthcare provider will test your blood glucose and A1C levels to get a range of your current blood sugar control.

As metformin is typically part of the first line of defense when treating type 2 diabetes, you may start out on a low dosage with regular monitoring to see if glucose control improves.

Precautions and Contraindications

Certain medical circumstances can make taking metformin risky or even prohibit its use, including:

• Kidney disease or kidney failure: Do not take Glucophage if you have severe renal impairment, as the drug poses a risk of lactic acidosis. This risk increases with the severity of kidney disease because metformin is excreted by the kidneys.
• Liver disease: Glucophage can decrease the liver's uptake of lactate, increasing lactate blood levels. Do not take Glucophage if you have liver impairment due to an increased risk of lactic acidosis.
• History of heart attack, severe infection, or stroke: These all increase the risk of lactic acidosis.
• Allergy or known hypersensitivity: Do not take Glucophage if you have a known sensitivity to metformin.
• Acute or chronic metabolic acidosis: Do not take Glucophage if you have metabolic acidosis, including diabetic ketoacidosis.
• Pregnancy: Metformin has been used to treat gestational diabetes. However, if you take metformin and are planning to become pregnant, you should discuss a plan for adjusting your diabetes treatment with your doctor.
• Breastfeeding: Metformin may enter breast milk, and there is a potential risk of low blood sugar in nursing infants.

Glucophage does not directly reduce blood sugar in the same manner as insulin. Therefore, it is typically not appropriate for people with type 1 diabetes who require insulin.

Dosage

Glucophage comes in 500, 850, and 1,000 milligrams (mg) tablets; glucophage XR comes in 500 or 750 mg tablets.

This medicine should be increased or titrated gradually to ease any stomach discomfort and to identify the lowest possible effective dose when it is first started. How long this takes depends on what your healthcare provider prescribes and how you respond to the medication.

For example, a person who is new to metformin and has been prescribed 2,000 mg might take the medication as follows:

• Week one: 500 mg with breakfast and 500 mg with dinner
• Week two: 1,000 mg with breakfast and 500 mg with dinner
• Week three: 1,000 mg with breakfast and 1000 mg with dinner, meeting their therapeutic goal

Those prescribed extended-release metformin typically begin with a starting once-daily dose of 500 mg and increase it by up to 500 mg each week.

A person who is prescribed 1,500 mg of extended-release metformin, for example, might take the medication as follows:

• Week one: 500 mg with dinner
• Week two: 1000 mg with dinner
• Week three: 1,500 mg with dinner

Throughout the duration of titration, your healthcare provider may ask you to monitor your blood sugar. If you experience hypoglycemia (low blood sugar) or any other side effects, contact your healthcare provider so that the medication can be adjusted accordingly.

If you miss a dose, try to take the missed pill as soon as possible, unless you're approaching the time of your next regular dose.

Do not double up on the medication dose.

Modifications

Your dosage may need to be modified by your healthcare provider if you have any pre-existing liver or kidney issues. In these cases, your symptoms and blood markers should be closely monitored.

Elderly patients should be kept on the lowest possible dose due to the potential for decreased kidney, liver, or heart function that may increase risk of lactic acidosis. Any dosage adjustment for those of advanced age should include a careful assessment of kidney function. 

How to Take and Store

To remember to take metformin, you should try to take it around the same time(s) every day.

It is recommended that people take Glucophage with food because this increases its absorption in the stomach and reduces side effects (e.g., stomach cramps, diarrhea, and nausea). The extended-release version is usually taken once per day with the evening meal.

Store this medication at a controlled room temperature (ideally 68 to 77 degrees F). You can travel with it at temperatures ranging from 59 to 86 degrees F.

Generally, try to avoid skipping meals or drinking alcohol while taking this medication.

Side Effects

Most of the side effects of metformin are mild.

Common

Common side effects of Glucophage include:

• Gas
• Diarrhea
• Stomach upset
• Metallic taste in the mouth

The first two typically top people's list of complaints about the drug. Gas and diarrhea can often be minimized by increasing the dose gradually. If you experience these side effects, contact your doctor to make sure that you are taking the medication correctly.

If you are experiencing persistent side effects and are not already on the extended-release version of this drug, consider asking your doctor about making the switch. The time-released delivery may help prevent gastrointestinal side effects.

Unlike many treatments for diabetes, Glucophage does not typically cause hypoglycemia. Also, unlike many type 2 diabetes medications, Glucophage does not cause weight gain and may even help with weight loss.

Severe

Lactic acidosis is a rare but serious side effect. Lactic acid builds up in the blood when the body has to metabolize sugars without adequate oxygen.

Although the latest studies suggest this may not be directly associated with metformin, the risk of lactic acidosis is increased in those with chronic kidney disease, liver, or heart disease.

If you experience any of the following, which includes symptoms of lactic acidosis as well as other serious reactions to metformin, seek medical help right away.

• A feeling of cold in your hands or feet
• Dizziness
• Lightheadedness
• Chest pain
• Extreme weakness or fatigue
• Unusual muscle pain
• Difficulty breathing or shortness of breath
• Sleepiness or drowsiness
• Stomach pains
• Nausea or vomiting
• Rash or hives

Warnings and Interactions

While you are taking metformin, your doctor will monitor your blood sugar levels and have you come in periodically for A1C testing to evaluate whether your dose or medication regimen needs to be adjusted. You may also need blood tests to monitor electrolytes and liver and kidney function.

Metformin may also result in a B12 deficiency due to a complication known as pernicious anemia that can lead to permanent neurological damage. B12 deficiency is also linked with an increased risk of strokes. Early symptoms of B12 deficiency may include anemia, ringing in the ears, and depression. It's important to have your B12 levels monitored since supplementation may be needed.

If metformin is inadequate to manage blood sugar, hyperglycemia (high blood sugar) may result. It's important to monitor blood sugar levels at home and to seek immediate medical care if you experience any signs of dangerously high blood sugar, which can lead to loss of consciousness. This may include confusion, seizures, dry mouth, vomiting, or sweet-smelling breath.

Metformin may interact with numerous medications, which may impact the medication effects or lead to serious complications. There are also risks with certain medical tests or procedures, so always inform your healthcare provider and dentist that you are taking Glucophage.

Serious interactions that may occur when using metformin include:

• Anti-diabetes medications or supplements: When Glucophage is taken with Glynase (glyburide), it may decrease blood levels of glyburide. When Glucophage is combined with supplements that target blood sugar, such as glymnema, blood sugar may drop too low.
• Radiological studies with contrast: Iodinated contrast materials, such as those used in computed tomography (CT) scans, combined with metformin can lead to a decrease in kidney function and lactic acidosis. You may be asked to stop taking Glucophage 48 hours before receiving iodinated contrast for a diagnostic test.
• Beta-blockers: If you're taking beta-blockers such as Lopressor (metoprolol) at the same time as metformin, the beta-blockers may prevent the fast heartbeat you typically feel when your blood sugar drops too low, virtually eliminating that warning sign.
• Dental or surgical procedures: Fasting from food or fluids during or in preparation for dental or surgical procedures while on metformin may increase the risk of complications, such as low blood pressure or renal impairment. You may need to temporarily stop taking the drug before your procedure.
• Congestive heart failure, heart attack, or sepsis: Metformin-associated lactic acidosis may occur with these and other conditions associated with hypoxemia (low blood oxygen levels). If one of these events occurs, you should stop taking the medication.
• Excessive alcohol intake: Frequently consuming alcohol or binge drinking large amounts on occasion may increase risks of lactic acidosis while on Glucophage.
• Diuretics: When Lasix (Furosemide), which is used to treat high blood pressure or edema, is taken with Glucophage the interaction that may raise blood levels of Glucophage and decrease levels of Lasix.
• Calcium-channel blockers: Adalat CC (nifedipine) used to treat high blood pressure or angina (chest pain) may increase absorption of Glucophage.
• Heart medications: Ranexa (ranolazine) may increase metformin and the risk of lactic acidosis.
• Tagamet (cimetidine): This drug used to treat ulcers and gastrointestinal reflux disease (GERD) is an H2 blocker that decreases the amount of acid made in the stomach. This can significantly increase blood levels of metformin, increasing the risk for lactic acidosis. Careful monitoring is needed if these drugs are taken together.
• Caprelsa (vandetanib): This drug, used to treat thyroid cancer, may increase metformin and the risk for lactic acidosis.
• Human immunodeficiency virus (HIV) medications: Integrase inhibitors, such as Tivicay (dolutegravir), that are used along with other medications to treat HIV may increase metformin levels and the risk for lactic acidosis.
• Carbonic anhydrase inhibitors: Drugs such as Topamax (topiramate) and Zonegran (zonisamide), used to treat seizures, Diamox (acetazolamide), used for glaucoma, and Keveyis (dichlorphenamide), for primary periodic paralysis (PPP) may cause hyperchloremic metabolic acidosis. This may increase the risk of lactic acidosis with Glucophage.

In addition, anyone taking drugs or supplements that can lead to high blood sugar or loss of blood sugar control should have their blood levels carefully monitored while on Glucophage. The same is true for anyone who stops these treatments while on Glucophage.

Medications and supplements that can lead to hyperglycemia or loss of blood sugar control include:

• Thiazides and other diuretics
• Corticosteroids
• Antipsychotics, such as phenothiazines
• Thyroid products
• Estrogens
• Oral contraceptives
• Anticonvulsants, such as Dilantin (phenytoin)
• Niacin (B3, nicotinic acid)
• Sympathomimetics
• Calcium-channel blockers
• Isoniazid used to treat tuberculosis (TB)

It's also important not to take more than one metformin medication at the same time unless advised to do so by a healthcare provider.

A Word From Verywell

While metformin is an excellent choice in addressing type 2 diabetes, lifestyle approaches such as a healthy diet and weight reduction (in those who are overweight) are the most important ways to manage insulin resistance and avoid the possible long-term consequences of diabetes. If Glucophage is prescribed to you, be sure to take it as prescribed and to check in with your doctor as recommended.