Metformin Side Effects and How to Manage Them

Metformin is a prescription drug in the biguanides class of medications. Like other biguanides, it can help lower blood sugar levels, highlighting its potential in managing type 2 diabetes. While generally well-tolerated, metformin may cause adverse side effects in some people, ranging from nausea and vomiting to more severe complications like an increased risk of lactic acidosis.

Understanding how metformin works and recognizing metformin side effects can help you mitigate discomfort and maximize the medication’s impact on blood sugar control. This article will explain the science behind metformin, its possible complications, and ways to manage any unwanted side effects.

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What Is Metformin and How Does It Work?

Metformin is an oral medication that can both treat and help prevent type 2 diabetes by managing high blood sugar levels. It’s often prescribed in tablet form but is also available in a liquid or sachets. Metformin primarily consists of metformin hydrochloride but also includes other inactive ingredients that help with the drug's stabilization and delivery.¹

So, how does metformin work? It helps your liver produce less glucose while lowering the amount of glucose you absorb from food and increasing your natural response to insulin (the hormone that controls the amount of glucose in the blood). Simply put, metformin helps people with high blood sugar lower their blood glucose levels to an optimal, safe range. It’s usually taken once daily with your evening meal, but your healthcare provider can offer dosing guidance.²

The U.S. Food and Drug Administration (FDA) has approved the use of metformin for treating type 2 diabetes, but this drug can still be prescribed off-label for people living with type 1 diabetes. Type 1 diabetes is an autoimmune disease that prevents the pancreas from producing insulin. To regulate blood sugar levels, insulin replacement therapy is required. In some cases, metformin may be prescribed alongside insulin therapy to help overweight people with type 1 diabetes manage their insulin resistance.

Also, metformin is sometimes prescribed to help manage gestational diabetes and polycystic ovary syndrome (PCOS). However, it hasn't officially been approved as a PCOS treatment by the FDA, so using it for this condition is considered off-label.³

Metformin Name Variations

Metformin belongs to a class of drugs called biguanides, a class of medications that can help lower blood glucose. Metformin is the only biguanide drug currently on the market, and it's available in other brand names, including: 

• Fortamet
• Glucophage
• Glucophage XR
• Glumetza
• Riomet
• Riomet ER

Common Side Effects of Metformin

The common side effects of metformin are generally mild and tend to occur when you first begin taking the antidiabetic medication. They typically subside as you continue treatment. However, if you do experience side effects from the drug, it'll likely be one or more of the following: 

• Heartburn
• Stomach pain
• Nausea
• Vomiting 
• Bloating
• Gas
• Diarrhea
• Constipation
• Weight loss
• Loss of appetite
• Headaches
• Weakness or fatigue
• An unusual metallic taste in the mouth

If you and your baby are healthy, taking metformin while pregnant or breastfeeding is generally considered safe, even if you're taking insulin. Additionally, research shows pregnant women may experience mild, stomach-associated side effects, such as nausea, vomiting, and diarrhea, more often while on metformin. But it's worth noting that these side effects are manageable.^{4, 5}

And here's a bit more reassurance: while metformin is transferred in small amounts into breast milk, research shows the drug hasn't been associated with any side effects in breastfed infants. Still, this doesn’t replace medical advice from your obstetrician.

Serious Side Effects of Metformin

While some cases of more severe side effects require medical attention, they're very rare and occur in less than 1 in 10,000 people. Some of the more serious side effects include:

• Lactic acidosis (or lactic acid build-up in the body)
• Muscle pain or cramping
• Anemia (or low red blood cell count)
• Hypoglycemia (or low blood sugar) 
• Vitamin B12 deficiency

Call your doctor or contact 911 immediately if you experience any of the following side effects: 

• Severe tiredness
• Fast or shallow breathing
• Slow heartbeat
• Whites of the eyes or the skin turn yellow⁶

Who Should Avoid Metformin?

Not everyone is a good candidate for metformin. Your healthcare professional may not prescribe you metformin and might suggest a different drug instead if you have any of the following conditions:

• An allergic reaction to metformin or other medicines
• Liver disease or kidney problems
• A severe infection
• A recent heart attack or heart failure
• Breathing or blood flow problems
• Drink a lot of alcohol
• Diabetic ketoacidosis

Your prescribing physician can offer individualized guidance based on your medical history and overall health goals. If metformin isn’t an appropriate medication choice for you, they may suggest other antidiabetic medications, like Ozempic.

4 Tips to Manage Metformin Side Effects

Many of metformin's common side effects affect the digestive system, and luckily enough, they are manageable with a few simple tricks. The way you take the drug can affect whether you get side effects, so, along with medical advice from your doctor, consider trying the following:

Begin With a Low-Dose

Most healthcare providers recommend starting with a low daily dose of 500 milligrams. Beginning with a low metformin dose and gradually increasing it over time can help minimize side effects. However, dosing requirements will vary between individuals based on age, sex, medical history, and health goals.

Use Metformin With Food

Food slightly delays the drugs' absorption, so taking metformin with breakfast, lunch, or dinner can help reduce your chances of an upset stomach, a common side effect of metformin. However, metformin on an empty stomach is still considered safe, and some foods should be avoided with metformin.

Switch to Extended-Release Metformin

Extended-release tablets (sometimes called "slow-release") release the drug into your bloodstream gradually, so you'll need to take fewer tablets daily. Extended-release metformin is often associated with fewer side effects. 

Take Metformin Tablets Whole

Never cut or crush your metformin tablets, as doing so can cause your body to absorb the drug too fast, which can lead to more dangerous side effects. If you have trouble swallowing the pills whole, talk to your healthcare provider about switching to metformin liquid or sachets instead of tablets.

Potential Metformin Drug Interactions 

Metformin may interact with some medications, including:

• Steroids such as prednisolone
• Diuretics such as furosemide
• Medicines that treat heart problems and high blood pressure
• Male and female hormones, such as testosterone, estrogen, or progesterone
• Other diabetes medicines

Always tell your doctor about any vitamins, supplements, and herbal remedies you're on before starting metformin (or any other medication, for that matter). Some supplements may worsen metformin side effects or interfere with its mechanisms. 

If you drink alcohol, discuss with your doctor if you're planning to take or are already on metformin. That's because drinking alcohol while on metformin can raise your risk of low blood sugar (clinically known as hypoglycemia) and lactic acidosis (lactic acid build-up in the blood).⁷

You'll also want to pay attention to your hydration levels when you're on metformin. Dehydration can cause acute kidney failure, which could lead to the accumulation of metformin in the body (since the kidneys remove metformin from the body). Too much metformin in your body can increase your risk of developing lactic acidosis, so stay well-hydrated while on metformin.⁸

Signs of lactic acidosis include nausea, vomiting, fatigue, fast and deep breathing, muscle cramps, body aches, drowsiness, confusion, lack of coordination, and low urine output. Seek medical attention immediately if you experience any of these symptoms.⁹

Learn More About the Signos CGM Program

Signos incorporates cutting-edge research and the proven power of continuous glucose monitoring. The data gleaned from the Signos app can help guide your health journey. Not sure if Signos is right for you? Take this quiz to find out! Interested in learning more about nutrition and healthy eating habits? Check out more articles on our blog.

Frequently Asked Questions

What Are the Toxic Side Effects of Metformin?

Some of the more severe side effects of metformin include severe tiredness, fast or shallow breathing, slow heartbeat, and the whites of the eyes or the skin turning yellow. Call your doctor or 911 immediately if you experience these side effects. 

What Should You Avoid While Taking Metformin?

Avoid drinking too much alcohol while taking metformin because alcohol can raise your risk of hypoglycemia (low blood sugar) and lactic acidosis (lactic acid build-up in the blood).

Why Do Doctors No Longer Prescribe Metformin?

Metformin is still prescribed by doctors; it's the most common medication used to treat type 2 diabetes. However, if you have severe kidney disease or decreased kidney function, your doctor may not prescribe you metformin, as the drug can contribute to lactic acidosis. 

What Is the Most Serious Adverse Reaction of Metformin?

While uncommon, lactic acidosis is metformin's most severe side effect. This is considered a "boxed warning," as the FDA requires metformin manufacturers to print a warning notifying users about this risk on the drug's label. Seek medical attention immediately if you experience any symptoms of lactic acidosis, such as nausea, vomiting, fatigue, fast and deep breathing, muscle cramps, body aches, drowsiness, confusion, lack of coordination, or low urine output.