Metformin is one of the most prescribed medicines on the planet, with more than 150 million people currently taking it for type 2 diabetes management (and, in some cases, weight loss).
While it is generally well tolerated, like all medications, it can have side effects.
In this article, we’ll look at how metformin works; its common, uncommon, and serious side effects; and how to alleviate those side effects.
Table of Contents
How metformin works
Metformin (brand names Glucophage, Glucophage XR, Fortamet, Glumetza, and Riomet, plus various generics) works by reducing the amount of sugar the liver releases throughout the day and increasing the body’s sensitivity to insulin.
It also reduces the amount of glucose (sugar) that is absorbed from the food you eat, which in turn reduces your blood sugar levels after eating.
Common side effects of metformin
The most common side effects of metformin include:
- Diarrhea (varying from mild to severe)
- Flatulence (passing gas)
- Nausea or vomiting
- Bloating and constipation
- Stomach discomfort
- Heartburn
- Headache
- Decreased appetite and weight loss
- Muscle pain or cramping
- A metallic taste in the mouth
Another common side effect of metformin is weight loss. Although the medicine is not FDA-approved for this use, it is frequently prescribed off-label for this purpose. In the Diabetes Prevention Program (DPP) Study, average weight loss among metformin users was approximately 4.4 to 6.6 pounds over two to three years.
See more in: Metformin and Weight Loss: Can a Pill Help You Lose Weight?
Foods to avoid while taking metformin
Experts don’t specifically recommend avoiding any particular foods while taking metformin to prevent gastrointestinal side effects such as diarrhea.
That said, there are certain foods and beverages that can increase the risk of these issues in general, so you may want to reduce your consumption of them if you are experiencing gastrointestinal discomfort with metformin. These include:
- Sugar
- Artificial sweeteners
- Dairy products
- Garlic, onions, and other foods high in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols — certain sugars that are poorly absorbed and may cause intestinal distress)
- Fructose (a natural sugar found in fruit)
- Gluten (a protein found in wheat, rye, barley, and their hybrids)
- Fried or fatty foods
- Spicy foods
- Alcohol
- Caffeine
These changes might help manage gastrointestinal symptoms such as diarrhea while taking metformin.
Learn more in: Can Metformin Cause Diarrhea? and Foods to Avoid While Taking Metformin.
How long after taking metformin do side effects start?
Metformin’s side effects usually appear quickly after the first dose, and while they improve for some people after a few weeks, others may find they persist.
Others may not even begin to experience side effects until they’ve been taking the drug for months or a year.
Uncommon (serious) side effects of metformin
Vitamin B12 deficiency
Recent research has shown that long-term use of metformin can result in vitamin B12 deficiency in some people. Symptoms of vitamin B12 deficiency can include:
- Anemia
- Inflammation of the tongue
- Fatigue
- Palpitations
- Pale skin
- Dementia
- Weight loss
- Infertility
Left untreated, B12 deficiency can cause significant nerve damage, ultimately leading to a diagnosis of peripheral neuropathy.
If a doctor isn’t aware of this risk, they could misdiagnose the cause of a person’s neuropathy as being the result of high blood sugar levels when it may in fact be a side effect of the B12 deficiency caused by metformin.
This nerve damage is irreversible, but further damage can be prevented by supplementing with a regular dose of vitamin B12.
Everyone taking metformin should have their B12 levels tested annually. In consultation with their healthcare provider, anyone with inadequate levels should start taking a B12 supplement immediately. (Vitamin B12 injections every few months may be recommended in some cases.)
Lactic acidosis
There have been a significant number of studies on metformin’s risk of causing lactic acidosis — a potentially fatal condition in which lactic acid builds up in the body. Symptoms of lactic acidosis can include:
- Nausea
- Vomiting
- Weakness
- Fatigue
- Fast, deep breathing
- Muscle cramps and body aches
Metformin comes with a “black box” warning about this risk, the most severe warning that the U.S. Food and Drug Administration (FDA) issues.
That said, a large-scale study reported in 2022 examined 4,241 cases of suspected metformin-associated lactic acidosis and found that only a small fraction (9 percent) had sufficient data to support such a diagnosis, underscoring the rarity of this condition.
Almost all cases of lactic acidosis from metformin use are results of overdoses — not normal use of the drug.
Those most at risk of developing lactic acidosis while on metformin include people with conditions such as kidney or liver issues, a history of heart attacks or acute heart failure, and frequent alcohol consumers.
See more in: Can Metformin Cause Lactic Acidosis?
Hypoglycemia (low blood sugar)
Metformin only very rarely causes hypoglycemia in people with diabetes who are not taking insulin injections, because it doesn’t increase insulin production like many other diabetes medications.
Call your doctor if you have any symptoms of hypoglycemia, which can include:
- Weakness
- Tiredness
- Nausea
- Vomiting
- Stomach pain
- Dizziness
- Lightheadedness
- Abnormally fast or slow heartbeat
“Fake” low blood sugar
While this isn’t a negative side effect, it’s an important situation to be aware of when starting on metformin.
When you drop your blood sugars to a “normal” range after running consistently high for a while, you may experience “fake” symptoms of low blood sugar.
Because your body has become used to high blood sugars, returning to normal levels may make you feel dizzy, lightheaded, nauseous, and extremely hungry.
This should pass after a few days to weeks as your body adjusts to your new normal blood sugar levels.
If you’re feeling low, always check your blood sugar to make sure you aren’t experiencing a real low blood sugar (typically considered to be below 70 mg/dl) that requires treatment with glucose.
Allergic reactions to metformin
Allergic reactions to metformin are rare, but they do happen. Symptoms of an allergic reaction can include:
- Rash
- Hives
- Itching
- Swelling of the face, lips, or tongue
- Difficulty breathing
If you experience any of these symptoms, seek medical attention immediately.
Reducing metformin side effects
Fortunately, there are a few things you can do to alleviate, lessen, or altogether prevent the side effects caused by metformin.
Take your dose during your meal, not before
One key step is to take your metformin dose halfway through eating your meal, rather than before you start eating.
People taking the medicine report far less stomach distress if there is already food in their stomach by the time their metformin dose is being digested.
Start with a very small dose
By starting with an extremely small dose, instead of the full dose your doctor would normally prescribe for your height and weight, you may be able to drastically reduce those initially uncomfortable side effects.
If this is an approach you’d like to try, talk to your doctor about adjusting your doses in order to give your body time to acclimate to the drug.
Read more in: Metformin Dosage Guide (Min and Max Doses).
Ask for the “extended-release” version
Too often, doctors prescribe the regular (standard- or immediate-release) version without any consideration for the extended-release (ER or XR) version.
When using the ER/XR version of metformin, the medication is gradually released over several hours instead of immediately. This process effectively lessens the unwanted gastrointestinal symptoms.
Although it may be more expensive, this approach can significantly decrease the overall side effects of metformin.
However, you may need to try the regular version first. This is so your doctor can tell your insurance company that you tried it and it wasn’t the right medication for you. Then they will be more likely to cover the extended-release version.
Take your dose whole
It is important not to crush, break, or chew your metformin tablets, as doing so could cause them to be absorbed more quickly and increase the risk of side effects.
Combine it with other diabetes medications
If your healthcare provider intends to start you on a GLP-1 drug, the side effects of metformin can actually help counterbalance the constipating side effects of many of the medicines in this class.
GLP-1 medications for diabetes currently available in the United States include the following:
- Dulaglutide (brand name Trulicity)
- Exenatide (Byetta)
- Exenatide extended release (Bydureon bcise)
- Liraglutide (Victoza, Saxenda)
- Lixisenatide (Adlyxin)
- Semaglutide (Ozempic, Rybelsus)
By including both types of drugs in your diabetes management plan, the side effects may help essentially balance each other out.
Read more in: Metformin Combination Drugs for Type 2 Diabetes.
Try something else
There are some people who simply do not tolerate metformin. If you find you cannot bear the side effects, talk to your healthcare team.
If you choose to stop taking metformin, they can help you find a different type of diabetes medication to manage your blood sugar levels.
Read more in: Stopping Metformin: When and How You Can Stop Taking Metformin and The Best Alternatives to Metformin for Type 2 Diabetes Management.
Who should avoid taking metformin?
As with all medications, there are certain people who shouldn’t take metformin.
The primary concern with metformin centers on its potential to increase the risk of excessive lactic acid production. Effectively removing lactic acid from the body requires proper functioning of the organs.
If you have been diagnosed with kidney or liver issues:
Your liver and your kidneys both play a critical role in clearing metformin from your body. If you have severe kidney or liver disease, you should not take metformin.
That said, recent guidelines have become more permissive relative to kidney disease, recognizing that metformin can be safe for use in people with mild to moderate chronic kidney disease (CKD) under certain conditions.
If you have mild to moderate CKD, speak with your doctor about whether metformin use is safe in your situation.
If you have had a heart attack or acute heart failure:
Serious heart conditions can affect how much blood is pumped to your kidneys, which can reduce your overall kidney function.
Because the kidneys play a crucial role in clearing metformin from your body, people with a history of heart issues should not take metformin.
If you drink alcohol often or in large quantities:
Given that metformin’s effectiveness depends on healthy liver and kidney function, regular heavy alcohol consumption can heighten the risk of complications when taking metformin.
Read more: Metformin & Alcohol: Can You Drink While Taking Metformin?
If you will be having surgery or an imaging test:
Lack of fluid and foods prior to surgery can increase the burden on the kidneys and raise the risk of high blood pressure. And the contrast dyes used in certain imaging tests such as MRIs can interact with metformin and cause a drop in kidney function.
Speak with your doctor about how to handle your metformin regimen if you will be having one of these procedures.
Learn more in: Is Metformin Safe?
Final thoughts
While metformin is generally well tolerated, it can have side effects just like any medication.
The most common side effects are mild and gastrointestinal in nature, but more serious side effects such as vitamin B12 deficiency and lactic acidosis can occur.
If you experience any symptoms while taking metformin, talk to your doctor about adjusting your dose, switching to extended-release tablets, or trying a different medication.
If you experience any serious or life-threatening symptoms, seek medical attention immediately.
Suggested next article: Everything You Need to Know About Metformin.
