7 Metformin Side Effects to Consider (Plus Fact vs. Fiction About The Risks of Long-term Use)

Many people with Type 2 diabetes take metformin to manage their blood glucose (sugar). It’s also sometimes prescribed off-label for prediabetes. When taken as prescribed, the benefits of metformin often outweigh its risks for most people. 

While some metformin side effects can be a hassle — especially when you first start taking it — they often improve over time. But what about long-term metformin risks? We’ll cover it all below.

Metformin side effects at a glance

Metformin side effects are typically mild. Examples include:

• Diarrhea 

• Nausea and vomiting

• Gas

• Heartburn

• Fatigue

• Headache

• Metallic taste in your mouth

Potentially severe metformin side effects are more rare, but possible. Examples include blood glucose (sugar) that drops too low (hypoglycemia) and low vitamin B12 levels. 

There’s also a boxed warning for high lactic acid levels (lactic acidosis). A boxed warning is the strictest warning from the FDA about a medication.

Let’s discuss eight metformin side effects in more detail.

EXPERT PICKS: WHAT TO READ NEXT

• Metformin vs. Metformin ER: Pharmacists list several considerations to think about before deciding which metformin form is best for you.

• Metformin alternatives: If metformin isn’t a good choice for you, several other medications are available to help you manage your diabetes.

• Metformin vs. Ozempic: Learn about the differences between these two diabetes medications, and when one may be better for you than the other (or when you may need both).

1. Diarrhea and gas

Diarrhea is the most common metformin side effect. Gas, bloating, and stomach discomfort are also possible. 

Researchers are still studying why these side effects are so common with metformin. One potential explanation is that metformin can change your gut microbiome — a unique blend of bacteria, viruses, and fungi that help us digest food and stay healthy. If this delicate balance shifts, it could lead to stomach problems.

For many people, these side effects improve over time. But for others, they may not completely go away. So what can you do if diarrhea continues after a few weeks of being on a steady metformin dose?

How to stop diarrhea from metformin

There are a couple ways to minimize diarrhea from metformin, including:

• Talk to your prescriber about switching to metformin extended-release (Glumetza, Fortamet). It’s considered less likely to cause diarrhea and an upset stomach than the immediate-release (IR) version. This is because metformin extended-release (ER) tablets release the medication more slowly into your body, making it less upsetting to the stomach.

• Changing your diet, at least temporarily. Some foods such as dairy products, spicy foods, and greasy foods can upset your stomach further and contribute to diarrhea. So avoiding these while you’re experiencing stomach problems can help prevent it from getting worse.

2. Nausea, vomiting, and heartburn

Nausea and vomiting is another common metformin side effect. Heartburn can also occur.

To minimize nausea and vomiting, try taking your metformin with a meal. You’re less likely to experience nausea if there’s food in your stomach. If you only take metformin once a day, take it with your biggest meal of the day. If you take it twice a day, try to take it with breakfast and dinner. And avoid lying down after you eat.

Like diarrhea, nausea and vomiting typically improve over time. However, If you’re still having stomach problems after a few weeks, talk to your prescriber. They may recommend a lower metformin dose to see if that helps. You may also be able to switch to metformin ER if you take the IR version, or consider another diabetes medication altogether.

3. Fatigue

Metformin may cause weakness and a lack of energy. This can affect your quality of life, especially if you’re already dealing with fatigue from diabetes itself.

There are several lifestyle tips you can consider to boost your energy. Examples include:

• Eating nutrient-dense foods, moving your body, and taking a power nap each day

• Make sure you’re getting enough sleep at night. Having good sleep hygiene habits can help with this. 

If these tips don’t help, talk to your prescriber. You may need a lower metformin dosage or a different medication altogether if your day to day life is impacted. Since weakness is also a symptom of hypoglycemia, it’s also a good idea to check your blood glucose if you’re feeling weak.

4. Weight loss

Some people lose weight while taking metformin. But for many people, it’s considered more of a benefit than a side effect.

When compared to some other diabetes medications, such as Ozempic (semaglutide) and Mounjaro (tirzepatide), metformin doesn’t cause as much weight loss. So if you have diabetes and weight loss is a goal of yours, talk to your prescriber about the best medication regimen for you.

5. Vitamin B12 deficiency

Metformin can interfere with the absorption of vitamin B12, a vitamin you need to maintain healthy blood cells. Low vitamin B12 levels, called vitamin B12 deficiency, may be more likely if you don’t eat enough B12. This is common for vegans and vegetarians, since vitamin B12 isn’t naturally found in plants.

Vitamin B12 deficiency can lead to anemia (low red blood cell count in the body). Symptoms of anemia include low energy, paleness, and dizziness.

While taking metformin, your prescriber may check your blood work to monitor your vitamin B12 levels periodically. If your levels drop, they may recommend taking a vitamin B12 supplement. In some cases, they may tell you to stop metformin if your vitamin B12 levels don’t improve.

6. Hypoglycemia

Metformin is used to lower blood glucose. But if it decreases too much, it can cause hypoglycemia (blood glucose less than 70 mg/dl) in rare cases. Hypoglycemia isn’t common with metformin on its own. But it’s more likely when you take it with other diabetes medications, especially insulin and sulfonylurea medications.

Combining diabetes medications like insulin and metformin is recommended for some people. If this applies to you, your prescriber will want you to monitor your blood glucose at home frequently. You should also be familiar with signs of hypoglycemia, such as sweating, shaking, and headaches. If you experience these symptoms, check your blood glucose.

If you take metformin, talk to your prescriber about how to handle hypoglycemia if it occurs. Typical treatment involves taking a fast-acting sugar source. You may also be advised to carry a glucagon or glucagon-like product that can quickly increase blood glucose.

7. Lactic acidosis

Lactic acidosis is a rare complication of metformin. Lactic acid is a substance our bodies use to create glucose. Since metformin helps prevent the creation of glucose, lactic acid may build up in the blood. When levels become too high, lactic acidosis can happen. It can be life-threatening if left untreated. Symptoms of lactic acidosis include:

• Rapid breathing

• Tiredness and weakness

• Fast heartbeat

• Confusion

Lactic acidosis rarely happens unless a person has taken too much metformin. Other conditions or situations can also put you at higher risk of experiencing lactic acidosis. Examples include being older than 65, having advanced kidney disease, or drinking excessive amounts of alcohol.

It’s important to keep up to date with all blood work that your prescriber orders for you. This will help them monitor your kidney and liver health, and make sure your risk of lactic acidosis is as low as possible.

Long-term metformin side effects, risks, and benefits: Separating fact from fiction

Generally, if you’re prescribed metformin, you’ll likely take it long-term. This may have you questioning the safety of long-term metformin use. While low vitamin B12 levels are a risk of long-term metformin use, several other risks (and benefits) discussed online aren’t always true. Here, we’ll address some common questions (and myths) around long-term metformin use.

1. Can long-term metformin use cause memory loss and dementia?

It’s unlikely that metformin causes memory loss. Some studies have highlighted a possible link between metformin and a higher risk of developing dementia. But most research has found the opposite: a possible lower risk of developing dementia in people with diabetes who take metformin. And one study found that people with diabetes who stopped metformin treatment had an increased risk of developing dementia.

It’s also important to note that diabetes itself likely increases your risk of dementia. This may be especially true if your diabetes isn’t well managed. So treating your diabetes effectively, often with medications like metformin, may help lower your risk of memory issues.

2. Can long-term metformin use cause kidney damage?

Metformin doesn’t cause kidney damage. But if your kidneys don’t function properly, there’s concern that metformin can build up in your system and cause lactic acidosis. This is a main reason why your prescriber will monitor your kidney function during your metformin treatment.

Keep in mind that unmanaged diabetes raises your risk of developing kidney problems. So metformin can actually help keep your kidneys and other organs healthy over time by treating diabetes.

3. Can long-term metformin use make PCOS worse?

No, metformin isn’t known to make polycystic ovary syndrome (PCOS) worse. Metformin is actually a treatment option for PCOS. And for people using metformin to treat PCOS, withdrawing metformin treatment has been found to cause weight gain and changes in how often you get a period.

4. Can metformin cause nerve damage?

It’s possible. Metformin may cause low vitamin B12 levels, which may lead to neuropathy (nerve damage).

However, diabetes that isn’t well managed can also lead to neuropathy. If you’re taking metformin for Type 2 diabetes and experience neuropathy, it may be a symptom of your diabetes rather than a side effect of the medication. Regardless, report any nerve pain you feel to your prescriber. They can help you evaluate the cause. 

5. Can metformin help you live longer?

It’s unclear if metformin can help you live longer. Though metformin has gained recent popularity for its potential to extend the lifespan, this claim isn’t supported by high quality research. However, research remains ongoing.

6. Can metformin lower the risk of cancer?

It’s possible that metformin may lower the risk of cancer. This may be by simply treating diabetes, as people with diabetes have a greater risk of certain cancers. But metformin may lower your cancer risk by other mechanisms, too.

7. Are metformin side effects different in men versus women?

Metformin side effects aren’t known to affect men and women differently. But there has been some research on whether metformin can cause sexual problems like erectile dysfunction (ED) in men. Some research suggests that metformin decreases testosterone — a hormone linked to male sexual health. But other research shows that metformin might improve blood flow to the penis, and can help treat ED.

We don’t have any long-term studies on metformin and sexual side effects in people with Type 2 diabetes. But what we do know is that having Type 2 diabetes increases your risk of ED, especially if it isn’t treated. If you’re considered to be obese or overweight, you’re also at a higher risk of developing ED.

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Written by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

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