Metformin is a prescription drug used alone or with other drugs to treat Type 2 diabetes. Along with diet and exercise, metformin helps reduce blood sugar. It’s available in generic form and under several brands by itself and in combination with other drugs. Common side effects include diarrhea, nausea and flatulence.
The U.S. Food and Drug Administration approved metformin in 1995 to treat Type 2 diabetes. It’s still the preferred first-line oral treatment for Type 2 diabetes and is the most prescribed drug to lower blood glucose worldwide.
From 2000 to 2015, doctors wrote about 553,291,094 metformin prescriptions in the United States, according to an article by Samantha Le and Grace C. Lee published in Clinical Drug Investigation in 2019.
Researchers first discovered the drug from an herb called Galega officinalis, also known as goat’s rue, in the early 1900s. But it took decades for it to be recognized as a viable treatment for Type 2 diabetes.
Metformin belongs to a class of drugs called biguanides. Metformin works to reduce blood sugar in three ways. It reduces glucose the body absorbs from food, reduces glucose made in the liver and increases the body’s response to insulin. Insulin is a substance in the body that controls the amount of sugar in the blood.
The most common metformin side effects affect the digestive system. Metformin was tested in a double-blind clinical trial with 141 patients who took metformin and 145 who took placebo.
The most common side effect in clinical trials was diarrhea, and about 53 percent of trial participants who took metformin experienced this side effect. Six percent of study participants who had diarrhea quit the study.
- Diarrhea - 53.2 percent
- Nausea/vomiting - 25.5 percent
- Flatulence - 12.1 percent
- Asthenia (weakness or lack or energy) - 9.2 percent
- Indigestion - 7.1 percent
- Abdominal discomfort - 6.4 percent
- Headache - 5.7 percent
Other side effects reported in one percent to 5 percent of participants include: abnormal stools, low blood sugar, body aches, lightheadedness, nail disorder, rash, increased sweating, taste disorders, chest discomfort, chills, flu-like symptoms, flushing and palpitations.
Is Metformin Safe?
Though metformin isn’t without side effects, most researchers agree that metformin has a good safety profile.
If you have severe renal impairment, a known hypersensitivity to the drug or have diabetic ketoacidosis, you should not take metformin. Metformin isn’t a treatment for Type 1 diabetes.
Metformin and Cancer
Metformin studies haven’t found that the drug can cause cancer. In fact, some studies claim metformin has anti-tumor properties.
One observational study from 2005 suggested that metformin could decrease the risk of cancer by 23 percent, according to a 2014 article by Samy Suissa and Laurent Azoulay in Diabetes Care. Since then, however, a review of the studies shows the anti-tumor effects in previous studies may have been exaggerated.
But in November 2019, the FDA announced it found that some batches of extended release metformin sold outside the United States contained small amounts of N-Nitrosodimethylamine (NDMA). NDMA can cause cancer in animals and may cause cancer in humans.
After the agency tested batches of metformin in the United States, it found some extended release batches contained unacceptable amounts of the toxic chemical. Several companies have since issued recalls.
Dosage, Interactions & Warnings
There is no set dosage for metformin. Medical providers will decide what dose is appropriate for a patient based on how a person reacts to the dose and how well it controls blood sugar.
Metformin comes in 500 mg, 850 mg and 1000 mg tablets. The recommended starting dose for adults is 500 mg twice a day or 850 mg once a day with meals. The maximum dose per day is 2,550 mg in divided doses.
It’s also available in extended release formulas of 500 mg and 750 mg.
People with kidney problems will take smaller doses.
Black Box Warning
Metformin has a black box warning for lactic acidosis — a condition where too much lactic acid builds up in the blood. It’s a serious problem and can lead to death.
If you experience these symptoms, seek medical attention right away.
- Abdominal or stomach discomfort
- Decreased appetite
- Fast, shallow breathing
- General feeling of discomfort
- Muscle pain or cramping
- Unusual sleepiness, tiredness, or weakness
This isn’t a complete list of metformin drug interactions. Make sure you tell your medical provider about all the supplements, medications and vitamins you are taking. Also tell them about any medical conditions you have.
- Furosemide – taking this drug with metformin increases the amount of metformin in the blood
- Nifedipine – this drug increases metformin absorption
- Drugs that affect the kidneys such as ranolazine, vandetanib, dolutegravir, and cimetidine can increase the exposure to metformin and increase the risk of lactic acidosis
- Alcohol – drinking excessively while taking metformin may increase risk for lactic acidosis
- Drugs that increase blood sugar may make metformin less effective. These include thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid
- Taking carbonic anhydrase inhibitors such as topiramate, acetazolamide or zonisamide with metformin can increase the risk of lactic acidosis
Warnings & Precautions
Certain people may be at greater risk for side effects while taking metformin. Older adults age 65 or over may be at greater risk for lactic acidosis.
Tell your doctor if you are a heavy drinker. Taking metformin while drinking alcohol can increase the risk of lactic acidosis.
Make sure you don’t miss any of your appointments to check your blood while on metformin. If you are going to have surgery or any major medical procedure, especially if contrast dye will be injected, you may need to stop taking metformin and wait at least two days before starting treatment again.
Recall & Lawsuits
In June 2020, the FDA announced five drugmakers issued voluntary recalls for certain extended release metformin drugs because of NDMA contamination. Apotex, Amneal, Maksans, Lupin and Teva issued voluntary recalls for certain lots.
Since then, several other companies have recalled lots of extended release metformin. Check the FDA’s website for the most recent recall updates.
As of Nov. 4, 2020, all recalls have been for extended release formulas, and regular metformin has not been affected. So far, brand name extended release metformin, Glucophage XR, has not been a part of the recall.
FDA does not recommend that patients stop taking recalled medications until their medical providers can give them a suitable replacement.
The FDA continues to investigate the problem. The FDA doesn’t believe that the active ingredient in metformin is responsible for causing NDMA formation, so it hasn’t required all manufacturers to issue recalls or market withdrawals.
In contrast, the FDA told manufacturers to withdraw all Zantac (ranitidine) products from the U.S. market. The agency found that NDMA levels in ranitidine could increase over time while sitting on a shelf or exposed to heat above room temperature. Dozens of people are now pursuing Zantac lawsuits after receiving a cancer diagnosis.
Some lawyers are currently accepting metformin lawsuits from people who developed cancer after taking the drug.
Prescription drug prices in the U.S. have been rising for several years. Some drugs in 2022 increased by more than $20,000 or 500%.
Between July 2021 and July 2022, there were 1,216 products whose price increases exceeded the inflation rate of 8.5% for that period. The average price increase for these drugs was 31.6%.
People who cannot tolerate metformin’s side effects have several medication options to choose from. Making lifestyle changes such as diet, exercise and losing weight may help control your blood sugar and reduce your need for medications.
|Hypoglycemia, nausea, weight gain
|Glucotrol (glipizide), Amaryl (glimepiride)
|Skin rash, hypoglycemia, weight gain
|Dipeptidyl-peptidase 4 (DPP-4) inhibitors
|Onglyza (saxagliptin), Januvia (sitagliptin), Trajenta (linagliptin)
|Headache, sore throat, upper respiratory infection
|Avandia (rosiglitazone), Actos (pioglitazone)
|Heart failure, fractures, heart attack, weight gain, fractures, increased risk of bladder cancer with Actos
|Sodium-glucose co-transporter 2 (SGLT2) inhibitors
|Invokana (canagliflozin), Farxiga (dapagliflozin), Jardiance (empagliflozin)
|Rare but serious genital infections, yeast infections, urinary tract infections
|Incretin mimetics (GLP-1 analogs)
|Byetta (exenatide), Trulicity (dulaglutide, Victoza (liraglutide)
|Increased risk of pancreatitis, increased risk of thyroid tumors, nausea or vomiting
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