What to Know About Biguanides (Metformin)

An Oral Medication Used to Treat Diabetes

Metformin pouring out of a bottle

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In This Article

Biguanides are a class of medications used to treat type 2 diabetes and other conditions. They work by reducing the production of glucose that occurs during digestion.

Metformin is the only biguanide currently available in most countries for diabetes treatment. Glucophage (metformin) and Glucophage XR (metformin extended-release) are well-known brand names for these drugs. Others include Fortamet, Glumetza, and Riomet. Metformin is also available in combination with several other types of diabetes medications, such as sulfonylureas.

Uses

Metformin is often prescribed for type 2 diabetes once the disease cannot be managed by lifestyle changes alone. If you've been diagnosed with type 2 diabetes and need medication to manage the disease, metformin is likely to be the first drug you'll take. As diabetes progresses, insulin injections may be needed to control blood sugar, but metformin may be continued to enhance your body's ability to use insulin.

Metformin works by controlling the amount of sugar in your blood. It does not affect how much insulin your body produces, but it increase sensitivity to insulin. This helps your cells take in glucose to use as energy, decreases the production of glucose in your liver, and reduces the concentration of glucose in your bloodstream.

Other Types of Biguanides

Biguanides were first derived from the French lilac, also called goat's rue (Galega officinalis). Some herbal remedies may include this plant. If you are using diabetes medications, tell your doctor about any herbal supplements you're taking to avoid interactions.

Phenformin was introduced in 1957 at the same time as metformin but then withdrawn in the late 1970s because it was associated with a fatal risk of lactic acidosis. Buformin was developed in Germany in 1957 but was never sold in the United States. It also was found to cause an increased risk of lactic acidosis. These forms of biguanides may still be available in some countries.

Other types of biguanides, called proguanil and chlorproguanil, are used as antimalarial drugs.

Off-Label Uses

Metformin may occasionally be prescribed off-label for type 1 diabetes, obesity, and polycystic ovarian syndrome (PCOS). It is also being investigated for potential cancer-fighting and cardioprotective benefits.

Before Taking

In addition to standard testing for diabetes, your doctor will test your kidney function to estimate glomerular filtration rate, or eGFR, before prescribing metformin for the first time.

Precautions and Contraindications

According to the American Diabetes Association guidelines, people with advanced kidney disease should not take metformin. However, for those with mild kidney impairment, and for some people with moderate kidney function, substantial evidence now suggests metformin combined with careful monitoring is beneficial.

If you drink alcohol frequently or tend to drink a lot at one time, share this information with your doctor before starting metformin. Since alcohol significantly lowers blood sugar, it may increase the risk of lactic acidosis as well as risky glucose imbalances.

If you easily become dehydrated during exercise or for other reasons, this is also important for your doctor to know, since dehydration increases the risk of lactic acidosis.

Warning signs of lactic acidosis include stomach pains, nausea, or vomiting; unusual muscle pain; sleepiness or fatigue; a slow or irregular heartbeat; and trouble breathing. If you experience any of these symptoms, seek immediate medical attention.

Women who are pregnant will be reassured to know that taking metformin during pregnancy is considered safe, and in fact, may help prevent complications. Women with PCOS also fare better when continuing to take metformin during pregnancy, according to studies.

May 28, 2020: The Food and Drug Administration (FDA) has requested that manufacturers certain formulations of metformin voluntarily withdraw the product from the market after the agency identified unacceptable levels of N-Nitrosodimethylamine (NDMA) in certain lots. Patients should continue taking their medication as prescribed until their health professional prescribe an alternative treatment, if applicable. Stopping metformin without a replacement can pose serious health risks to patients with type 2 diabetes.

Dosage

Metformin is taken at doses of 500 to 2550 milligrams a day. Your doctor will start your prescription at a low dose and gradually increase it according to your body's needs. Depending on the form, it is taken once to three times daily.

How to Take and Store

Metformin is an oral medication that can be taken as a tablet or liquid. Inhaled forms are also now available. Instructions must be followed for the safe use of each product. It can safely be stored at room temperature.

Metformin should be taken with meals to prevent side effects. If you forget a dose, take your next dose at the usual time rather than double up. If you accidentally take too much, seek medical attention: It's important to stabilize your blood sugar right away to avoid serious health issues.

Side Effects

Metformin does not cause excessive hypoglycemia, which is an advantage over some other diabetes medications. It also doesn't cause weight gain, and it has benefits for some cardiovascular risk factors. It may even help with weight loss and lowering cholesterol.

Common

Metformin can cause nausea, upset stomach, and diarrhea, particularly when you first start taking it. It should always be taken with food to reduce the risk of gastrointestinal issues.

Over time, taking metformin may block vitamin B12 absorption in the body. Ask your doctor whether B12 vitamin supplements are right for you.

Severe

People with severe kidney impairment or heart failure should not take metformin since in rare cases it can cause lactic acidosis. The risk is very low—around one in 30,000 people taking metformin—but the condition can be fatal.

Warnings and Interactions

While metformin is generally well tolerated and has a good safety profile, if you combine this medication with others such as insulin or sulfonylureas, you'll need to work with your doctor to be especially careful about side effects such as low blood sugar. Report any changes or unusual symptoms to your health care provider right away when you're combining metformin with other medications.

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  1. American Diabetes Association. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2019. Diabetes Care. 2019 Jan;42(Suppl 1):S90-S102.

  2. Metformin. MedlinePlus, U.S. National Library of Medicine. 2018.

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