What are the most common side effects of metformin?
LAST UPDATED: Nov 15, 2020
7 MIN READ
HERE'S WHAT WE'LL COVER
Metformin (brand name Glucophage) has been a first-line treatment for type 2 diabetes since the mid-90s. In that time, it's gained a good reputation in the medical community for having positive effects on a lot more than just diabetes. It's associated with weight loss, used to treat polycystic ovary syndrome (PCOS), and it may play a role in cancer prevention, to name a few (Markowicz-Piasecka, 2017).
Before running to your healthcare provider to ask for a prescription, however, it's important to be aware of this powerful drug's common side effects and contraindications.
Common side effects of metformin
The most common side effects of metformin are gastrointestinal (GI) issues, such as nausea, diarrhea, vomiting, heartburn, loss of appetite, stomach pain, stomach upset, and a metallic taste in the mouth (Bonnet, 2016). Studies show that up to 25% of people experience these side effects, but they are usually relatively mild and tolerable (McCreight, 2016). About 5% of people have GI symptoms that are bad enough to stop taking metformin.
Here are some possible ways to lessen these issues:
Taking metformin with food may decrease GI symptoms.
It may help to start on a lower dose and slowly increase it, rather than starting on a higher dose right away.
There seems to be good evidence that the extended-release formula reduces GI side effects (Blonde, 2004). You may want to discuss this option with your healthcare provider.
Here's a closer look at these and other potential metformin side effects:
Of all the GI symptoms that can happen with metformin, the most common is diarrhea. Over 60% of patients who experience GI symptoms on metformin have diarrhea (Fatima, 2018). We don't know the exact reasons for this, but a couple of possibilities are that metformin leads to higher serotonin signaling levels and lower absorption of bile salts in the gut. These actions increase muscular contractions in the gut and pull more fluids into the GI tract—the perfect recipe for diarrhea.
Even without taking metformin, about 20% of people with type 2 diabetes suffer from diarrhea (Gould, 2009). When metformin is added into the mix, diarrhea rates in this population can be as high as 50%.
Vitamin B12 deficiency
While not as common as diarrhea, metformin can also cause vitamin B12 deficiency in up to 20% of patients (de Jager, 2010). Vitamin B12 is important for many processes in the body, including neurologic function, so your healthcare provider will likely monitor your vitamin B12 levels if you take metformin (Langan, 2017). Don't worry, though—if you do develop a deficiency, it's easy to treat with a vitamin B12 supplement.
Can metformin cause weight loss? There is some evidence that it might, though it should not be seen as a miracle weight loss drug (Apolzan, 2019). In one study, metformin caused higher rates of weight loss at one year than placebo, but at lower rates than patients who implemented intensive lifestyle interventions (such as dietary changes, physical activity, and other lifestyle changes). Long-term, though—after 6–15 years—those who'd lost weight on metformin were much more successful at maintaining their weight loss than the other two groups.
One of the benefits of metformin for patients with diabetes is that, at the very least, it does not appear to cause weight gain. The same cannot be said for two of the other most commonly prescribed types of diabetes medications: insulin and sulfonylureas—both of which can cause dramatic weight gain (Provilus, 2011). The most common examples of sulfonylureas (a class of anti-diabetes drugs) are glimepiride (brand name Amaryl), glipizide (brand name Glucotrol), and glyburide (brand name Glynase).
A rare but serious complication that may be associated with metformin (particularly in people with advanced liver or kidney disease) is a condition called lactic acidosis (Foucher, 2020). Lactic acidosis is when there's a buildup of lactic acid in the blood, often causing liver or kidney failure. Even in patients with mild to moderate chronic kidney disease, however, metformin is generally safe, with some precautions (MacCallum, 2019).
Lactic acidosis with metformin is so rare that some researchers question if it's really something to be so concerned about at all (Misbin, 2004).
What is metformin used for?
Metformin is, first and foremost, an antidiabetic drug used to treat type 2 diabetes (Lv, 2020). You might know it as Glucophage, which is one of the brand names for metformin (US. National Library of Medicine, 2018). Other brand names include Glumetza, Riomet, and Fortamet.
In more recent years, healthcare providers have also used metformin off-label to treat polycystic ovary syndrome (PCOS), a condition associated with infertility, early pregnancy loss, gestational diabetes, and other hormonal symptoms (Markowicz-Piasecka, 2017). While metformin is helpful with PCOS symptoms, it's not currently FDA-approved for the treatment of PCOS.
There's some evidence suggesting that metformin might positively affect other disease processes such as cancer, aging, and cardiovascular disease. This evidence is not conclusive, and metformin is not FDA-approved for any conditions other than type 2 diabetes.
We do have promising evidence that metformin can be used to treat prediabetes (Lilly, 2009). Prediabetes is when blood sugar levels are borderline but not quite to the level of full-blown diabetes. Metformin can be used to prevent a patient with prediabetes from progressing to type 2 diabetes.
What is diabetes?
So, what is diabetes exactly? Generally, when we talk about diabetes, we're referring to diabetes mellitus (not to be confused with diabetes insipidus, a completely different disease). Diabetes mellitus is a metabolic disease that involves blood sugar levels that are higher than they should be (Sapra, 2020).
There are several varieties of diabetes mellitus, but the two main types are:
Type 1 diabetes
Type 1 is commonly referred to as "juvenile diabetes" since it mostly shows up in children and adolescents. Type 1 diabetes happens when the body's natural insulin secretion is not working properly—that's why patients with type 1 diabetes always require insulin. Type 1 diabetes is not treated with metformin.
Type 2 diabetes
Type 2 is generally an adult-onset disease (though it shows up in younger patients). Unlike type 1 diabetes, type 2 is due to insulin resistance, which means that the cells don't properly respond to insulin, resulting in high blood sugar. There are genetic and behavioral risk factors, and it is more prevalent in people with obesity. Patients with type 2 diabetes sometimes need insulin, but not always. Metformin is one of the mainstays of treatment for type 2 diabetes, along with lifestyle changes.
How does metformin work for type 2 diabetes?
Metformin is in a class of drugs called biguanides, and it's an effective anti-diabetes drug (Markowicz-Piasecka, 2017).
The way this works is that high blood sugar is a primary marker of type 2 diabetes, and metformin lowers the body's blood glucose levels—the concentration of sugar in the blood. It does this by decreasing glucose production by the liver. Metformin is mostly absorbed in the small intestine (hence, all those GI symptoms).
There are both immediate-release and extended-release versions available. The extended-release tablets are often preferred because they have a better side effect profile than the immediate release formula (Jabbour, 2011). This is particularly helpful for patients who experience severe GI symptoms from the immediate-release version.
How safe is metformin?
Metformin is often a preferred anti-diabetes treatment because it is quite safe and well-tolerated by most patients (Diabetes Prevention Program Research Group, 2012). There was some potential concern about how safe metformin is for adults over the age of 80, but more research is needed on that subject (Schlender, 2017).
There's even evidence that metformin decreases diabetes-related deaths and deaths from all other causes, compared to the placebo group (Markowicz-Piasecka, 2017).
Some patients should not take metformin—specifically, patients with advanced kidney disease or liver failure. These patients are at a much higher risk of developing lactic acidosis. Mild to moderate levels of kidney or liver disease are generally fine with metformin.
Can you just stop taking metformin?
Stopping any medication should be done under the care of a healthcare professional. There is no danger in stopping metformin, but any positive effects you might have had while on the drug will go away when you stop taking it.
Contraindications of metformin
While metformin is a safe and effective medication for most people, certain people should not take metformin. Contraindications include severe kidney disease, advanced liver disease, and a history of lactic acidosis while on metformin.
If you have one of these contraindications, your healthcare provider will work with you to find the best alternative treatment options.
Healthcare providers used to steer away from prescribing metformin to patients with any level of kidney disease or impairment. In recent years, though, it's become clear that metformin is generally safe in those with mild to moderate kidney problems (Tanner, 2019). Metformin is only contraindicated in severe cases (stage 3 or 4) of kidney disease when kidney function is dangerously low since those patients are at elevated risk of developing lactic acidosis.
There has been some concern in the past about prescribing metformin to patients with liver disease. For most patients with liver disease, though, it is safe and can even be beneficial (Brackett, 2010). This is especially true for those with non-alcoholic fatty liver disease, which is the most common form of liver disease in the U.S.
Patients with advanced cirrhosis may need to be monitored closely or avoid metformin altogether since cirrhosis is a serious risk factor of developing lactic acidosis. If you have liver disease, discuss this with your healthcare provider before starting on metformin.
History of lactic acidosis while taking metformin
Lactic acidosis is a rare but very dangerous complication associated with metformin. You should not take metformin if you've ever developed lactic acidosis while on this drug or if you are at an increased risk of lactic acidosis.
Contrary to previous assumptions, having a history of heart disease or heart failure is not a contraindication for taking metformin (Tahrani, 2007). In fact, it may be beneficial in improving symptoms of congestive heart failure, which is highly prevalent in patients with type 2 diabetes mellitus. There used to be some concern that heart failure or a history of heart attack increases the risk for lactic acidosis, but there's no solid evidence of that.
Metformin drug interactions
Before starting on metformin, it's important to tell your healthcare provider about any other medications you are taking. There are several serious drug interactions, including:
Excessive alcohol consumption
Iodine contrast (used in imaging tests)
Certain anticancer drugs
There are several other drug interactions that may require some additional monitoring, so be open and honest with your healthcare provider about all drugs you are taking—both medical and recreational (Maideen, 2017). As with any drug, stop taking metformin if you experience an allergic reaction to it, and let your healthcare provider know right away.
Discuss concerns with your healthcare provider
Potential side effects can be one of the scariest parts of starting on a new medication if you don't know what to expect. Now that you have a good understanding of what side effects you might encounter with metformin, we recommend discussing any specific concerns with your healthcare provider.
If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.
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