Key takeaways:
Metformin is approved to treat Type 2 diabetes. It’s also prescribed off-label for other uses, including prediabetes.
Common metformin side effects include diarrhea, nausea, and vomiting. It can also cause fatigue, weight loss, and low vitamin B12 levels.
While uncommon, metformin can also cause blood glucose (sugar) to drop too low and lactic acidosis. In severe cases, these side effects are medical emergencies.
Long-term metformin use isn’t known to cause dementia or kidney damage, or to worsen polycystic ovary syndrome (PCOS). And it’s not known if metformin can help extend life expectancy. Some evidence suggests that it may lower the risk of cancer and dementia in people with diabetes.
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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 the 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 and improve over time. While less common, more serious side effects and risks are also possible.
Mild metformin side effects include:
Diarrhea
Nausea and vomiting
Gas
Heartburn
Fatigue
Headaches
Metallic taste in the mouth
Potentially serious metformin side effects include:
Blood sugar that drops too low (hypoglycemia)
Low vitamin B12 levels
Lactic acidosis, which it carries a boxed warning for
Let’s discuss seven metformin side effects in more detail.
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 you digest food and stay healthy. If the balanced composition of your gut microbiome shifts, it can lead to stomach problems.
For many people, these stomach-related metformin side effects improve over time. But for others, they may not completely go away. So what can you do if diarrhea, for example, continues after a few weeks of being on a steady metformin dosage?
How to stop diarrhea from metformin
There are a couple ways to minimize diarrhea from metformin, including:
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. Avoiding these foods while you’re experiencing stomach problems can help prevent them from getting worse.
2. Nausea, vomiting, and heartburn
Nausea and vomiting are other common metformin side effects. Heartburn can also occur.
To minimize nausea and vomiting, try taking metformin with a meal. You may be 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 these stomach problems after a few weeks, talk to your prescriber. They may recommend a lower metformin dosage to see if that helps. You may also be able to switch to metformin ER if you take the IR version. Or you may want to 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
Making sure you’re getting enough sleep at night, which could mean reviewing your sleep hygiene habits
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 sugar if you’re feeling fatigued.
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 get enough B12 in your diet. 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). Symptoms of anemia include low energy, paleness, and dizziness.
While you’re taking metformin, your prescriber may want you to periodically have blood work to monitor your vitamin B12 levels. If your levels drop, they may recommend taking a vitamin B12 supplement. If your vitamin B12 levels don’t improve, they may tell you to stop taking metformin.
6. Hypoglycemia
Metformin is used to lower blood sugar. But in rare cases, it can cause hypoglycemia (blood sugar less than 70 mg/dL). Hypoglycemia, or blood sugar that’s too low, isn’t common with metformin on its own. But it’s more likely if you take metformin with other diabetes medications, especially insulin or 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 sugar 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 sugar.
Even if you’re taking metformin on its own, talk to your prescriber about how to handle hypoglycemia if it occurs. Typically, treatment involves ingesting a fast-acting sugar source. You may also be advised to carry a glucagon or glucagon-like product that can quickly increase blood sugar.
7. Lactic acidosis
Metformin has a boxed warning, the FDA’s strongest medication warning, about the potential for lactic acidosis.
Lactic acid is a substance our bodies use to create sugar. Since metformin helps prevent the creation of sugar, lactic acid may build up in the blood. When levels become too high, lactic acidosis can happen. This condition 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. But there are other factors that can 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 any 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
Metformin is often prescribed for long-term use, which can raise questions about its safety. While low vitamin B12 levels are a risk of long-term metformin use, not all of the risks (or benefits) people associate with metformin are based on fact.
Here, we’ll address some common questions (and myths) around long-term metformin use.
Can long-term metformin use cause memory loss or dementia?
It’s unlikely long-term metformin use causes memory loss or dementia. A few studies have suggested a possible link. But most research shows that metformin use in people with diabetes is associated with a lower risk of dementia.
It’s also important to note that diabetes itself likely increases a person’s risk of dementia. This may be especially true when the condition isn’t well managed. So treating diabetes effectively, which often involves taking a medication like metformin, may help lower the risk of memory issues.
Can long-term metformin use cause kidney damage?
No, metformin doesn’t cause kidney damage. But if your kidney function is significantly reduced, metformin can build up in the body, increasing the risk of lactic acidosis. This is why your kidney function is monitored during treatment.
Keeping your blood sugar levels in check with metformin may actually help protect your kidney health over time.
Can long-term metformin use make PCOS worse?
No, metformin isn’t known to make polycystic ovary syndrome (PCOS) worse. In fact, it’s commonly used to help manage PCOS by improving insulin resistance. This may help with weight management, menstrual regularity, and ovulation.
Can metformin cause nerve damage?
It’s possible for metformin to indirectly contribute to nerve damage in some cases. Long-term metformin use can lower vitamin B12 levels, which may lead to nerve-related symptoms. However, unmanaged diabetes is also a major cause of nerve damage. So any new or worsening nerve symptoms should always be discussed with your care team.
Can metformin help you live longer?
It’s unclear if metformin can help you live longer. Though metformin has recently been touted for its potential to extend lifespan, this claim hasn't been supported by high quality research. However, research remains ongoing.
Can metformin lower the risk of cancer?
It’s possible that metformin may lower the risk of cancer for some people. This may be by simply treating diabetes, as people with diabetes have a greater risk of certain cancers. But metformin may lower cancer risk via other mechanisms, too.
Are metformin side effects different in men and women?
Men and women don’t generally seem to experience different side effects from metformin. 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.
There haven’t been long-term studies on metformin and sexual side effects in people with Type 2 diabetes. But it’s important to note that diabetes and excess body weight themselves are significant risk factors for ED.
Frequently asked questions
Metformin isn’t known to be hard on the organs. However, if you have existing kidney problems, certain metformin side effects may be more likely. This is because metformin can build up in the body if your kidneys aren’t able to get rid of it properly.
Other health conditions, such as liver disease and heart failure, can also increase your risk of lactic acidosis, a potentially severe but rare metformin side effect. Let your prescriber know your full health history before starting metformin.
Foods that are high in fat and sugar can prevent metformin from working as well as it could to lower your blood sugar. This includes processed and packaged foods, such as white bread, chips, and sugary cereals. It’s also a good idea to limit your saturated fat intake, which means reducing your consumption of foods like red meat and butter.
It’s also best to limit alcohol, since it can put you at greater risk of hypoglycemia and lactic acidosis. Alcohol can also increase your risk of high blood pressure and weight gain, which can be problematic if you have diabetes.
It’s OK to drink coffee while taking metformin, but stick to a reasonable amount and avoid sugary coffee drinks. For the average adult, 400 mg of caffeine per day (4 to 5 cups of coffee) is the recommended maximum. But if you have diabetes, your healthcare team may recommend consuming a smaller amount.
Metformin isn’t known to be hard on the organs. However, if you have existing kidney problems, certain metformin side effects may be more likely. This is because metformin can build up in the body if your kidneys aren’t able to get rid of it properly.
Other health conditions, such as liver disease and heart failure, can also increase your risk of lactic acidosis, a potentially severe but rare metformin side effect. Let your prescriber know your full health history before starting metformin.
Foods that are high in fat and sugar can prevent metformin from working as well as it could to lower your blood sugar. This includes processed and packaged foods, such as white bread, chips, and sugary cereals. It’s also a good idea to limit your saturated fat intake, which means reducing your consumption of foods like red meat and butter.
It’s also best to limit alcohol, since it can put you at greater risk of hypoglycemia and lactic acidosis. Alcohol can also increase your risk of high blood pressure and weight gain, which can be problematic if you have diabetes.
It’s OK to drink coffee while taking metformin, but stick to a reasonable amount and avoid sugary coffee drinks. For the average adult, 400 mg of caffeine per day (4 to 5 cups of coffee) is the recommended maximum. But if you have diabetes, your healthcare team may recommend consuming a smaller amount.
The bottom line
Common metformin side effects include diarrhea, nausea and vomiting, and fatigue. Weight loss and low B12 levels may also occur. Usually, metformin side effects are temporary and can be managed at home. However, serious side effects, such as very low blood sugar (hypoglycemia) and lactic acidosis, are possible.
There are several common myths about long-term metformin use — such as the medication causing dementia or kidney damage. Meanwhile, other claims about metformin, like that it can help you live longer or cause sexual problems in men, need to be researched further.
Why trust our experts?
References
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