Metformin Side Effects: What Are They?

Metformin (Glucophage, Fortamet, others) is a common medication used to treat type 2 diabetes.

It is a first-line treatment choice for patients who are 10 years of age and older with diabetes, according to the American Diabetes Association.

Metformin may also be used for gestational diabetes, polycystic ovary syndrome (PCOS), and the prevention of type 2 diabetes/prediabetes.

Common side effects of metformin can include dizziness, irregular heartbeat, feeling cold, tiredness, and more.

In this article, we’ll explore side effects, long-term effects, and provide a complete dosage guide. We’ll also discuss how to manage side effects and potential drug interactions to watch out for.

Metformin Side Effects

Metformin is a medication that is in a class of drugs known as biguanides.

It helps normalize blood glucose levels in the body for people who have high blood sugar. It is approved by the U.S. Food and Drug Administration (FDA) for treating type 2 diabetes.

Metformin can cause mild side effects that are more common, but may also cause some serious side effects.

Common Side Effects of Metformin

Metformin side effects that are mild will typically go away as your body gets used to the medication.

Any side effects that do not resolve, or get worse over time, should be reported to a medical provider.

Common side effects of metformin include:

• Nausea: One of the most common side effects of metformin, nausea effects will typically wear off when you are used to the drug. To help decrease nausea, take metformin with a meal.

• Diarrhea: Another extremely common side effect, diarrhea occurs because metformin changes the way that glucose is absorbed in the intestines. The result of this process leads to lactic acid formation, which can be an irritant to the intestinal system, resulting in diarrhea. Most healthcare providers start patients on low doses of metformin initially, so that the body can gradually get used to this process without having an extreme reaction.

• Bloating and gas: These side effects also occur in response to intestinal irritation. Taking metformin with food can help, and the effects may lessen over time.

• Weight loss: While metformin is not a weight loss drug, because it decreases how much blood sugar is in the body, it can help to normalize the relationship between insulin and glucose. Instead of extra glucose being stored in fat cells, it leaves the body, which can result in some weight loss.

• Headache: Metformin works by preventing glucose production in the liver. Headaches can happen as a result of changes to the way the body metabolizes medication or because of changes to glucose levels that the body is used to. Tell your medical provider if the headaches last a long time or are more than mild.

• Metallic taste in mouth: While less common, around 3 in every 100 people who take metformin may experience a temporary metallic taste in the mouth. It is not a long-lasting side effect.

Severe Side Effects of Metformin

While metformin has many positive effects, it can cause some serious side effects, including the following:

• Anemia: Metformin can interfere with the body’s ability to absorb vitamin B12, which plays an important role in healthy red blood cells. If this happens, it can lead to anemia, which may cause symptoms like extreme tiredness, feeling cold all the time, and dizziness. Vitamin B12 deficiency, over time, can cause symptoms like numbness and tingling, mood changes, brain fog, poor energy, and hair loss. If you notice signs of anemia, a healthcare provider can run basic lab tests to check your red blood cells and iron levels. People who follow vegetarian or vegan diets, or who do not get enough vitamin B12 or calcium in their diets are more likely to experience anemia as a side effect of metformin.

• Hypoglycemia: Metformin itself does not cause hypoglycemia, but if it is combined with strenuous exercise, other diabetes medication that also lowers blood sugar levels, an imbalanced diet, or excessive alcohol intake, hypoglycemia can occur. Symptoms of hypoglycemia include tiredness, weakness, lightheadedness, nausea, vomiting, and a heart rate that is either too fast or too slow.

• Lactic acidosis: This side effect is very rare, but very serious if it occurs. Metformin carries an FDA black box warning for this risk. It occurs when too much metformin builds up in the body, leading to high levels of lactic acid in the body. Signs of lactic acidosis are a medical emergency and must be treated immediately since it can be life-threatening. Symptoms of lactic acidosis include extreme tiredness, decreased appetite, nausea, vomiting, trouble breathing, dizziness, lightheadedness, feeling cold, muscle pain, a heart rate that is too fast or too slow, flushing (sudden reddening) or feelings of warmth in the skin. 

If you notice signs or symptoms of anemia or hypoglycemia, speak with your healthcare provider.

If you notice signs of lactic acidosis, get emergency medical care right away. While rare, metformin-associated lactic acidosis can be fatal if not treated promptly.

If you have questions about how to safely take metformin, ask your healthcare provider. This will help offset potential future complications and side effects.

Long Term Effects of Metformin

Most people who are prescribed metformin take it long-term.

Type 2 diabetes is a chronic condition that often needs long-term intervention to control.

There are some long-term effects of metformin that are backed by research, but other concerns do not have evidence from trials to back them up.

If you are concerned about the long-term effects of metformin, speak with your healthcare provider.

Long-term effects that are backed by research include:

• Lower risk for cancer: Few people will complain about a reduced risk for cancer. People who have diabetes may be 1.5 to 2 times more at risk for certain types of cancer, such as breast cancer, bladder cancer, and colorectal cancer. Research points to potentially protective effects of metformin against cancer, reducing the risk between 30% and 50%. While research is not fully clear on how metformin protects against cancer, one theory is that metformin slows or stops the ability of cancerous tumors to grow.

• Anemia: A potential side effect of metformin in either short or long-term treatment, anemia can lead to many health complications that reduce the quality of life. Your medical provider may check your lab levels regularly to ensure that you do not develop anemia. They may also recommend certain dietary changes or supplements to offset imbalances, like vitamin B12, folic acid, calcium, iron, or other nutrients. If you are diagnosed with anemia from low B12 levels, a healthcare provider may prescribe vitamin B12 shots to restore your levels more quickly.

Effects of Metformin During Pregnancy

Metformin may be safely used in pregnancy or breastfeeding. While metformin can cross the placenta, studies have not found complications for fetal development or other negative pregnancy outcomes. 

Controlling type 2 diabetes or gestational diabetes is important since the effects of high glucose on fetal development can be harmful. In extreme cases, very high levels of glucose can lead to fetal demise.

Other research has found that metformin may also reduce the rate of miscarriage for people who have PCOS.

Metformin Dosage Guide

Metformin is available in immediate-release and extended-release forms. It may be taken as a tablet or oral solution.

The dosage of metformin depends on the reason it was prescribed, the age of the patient, and other health factors. Typical dosages may include:

• Extended-release tablets: Initially, 500-1,000 mg per day, typically taken with the evening meal. Doses may be gradually increased to 2,000-2,500 mg per day.

• Extended-release suspension: Initial dose 5 mL. Doses may be slowly increased up to a maximum of 20 mL per day.

• Oral solution: Initially, 5 mL twice daily or 8.5 mL once per day, taken with meals. Maximum dose is typically 25.5 mL per day.

• Oral tablets: Initial dose is 500 mg two times per day, taken with morning and evening meals. It may also be given as 850 mg daily with the morning meal. Dosage may be increased over time to a maximum of 2,550 mg per day in divided doses.

If you miss a dose or forget to take metformin, take it as soon as you remember. If it is almost time for your next regularly scheduled dose, do not double up.

Skip the missed dose and resume your normal schedule.

Keep metformin at room temperature. Do not expose it to heat, light, or moisture. Do not allow it to freeze.

Managing Side Effects

Metformin typically causes fewer side effects as your body adjusts to the medication.

To minimize side effects, your healthcare provider may:

• Start you on a low dose
• Have you take metformin with meals
• Prescribe extended-release metformin so you take it less frequently

Because lactic acidosis is a rare but potentially life-threatening complication of metformin, your medical provider may advise that you avoid alcohol since it can increase the chances of developing this condition. 

Other factors that increase the risk for lactic acidosis include:

• Liver problems
• Kidney problems
• Heart problems like acute heart failure or recent heart attack

Metformin Drug Interaction Risks

Metformin interacts with certain drugs. Inform your healthcare provider and pharmacist of any other medications, OTC medicines, or dietary supplements that you take.

This will help prevent interactions and avoidable side effects.

Metformin interacts with the following:

• Cimetidine
• Digoxin
• Dofetilide
• Morphine
• Procainamide
• Quinidine
• Ranitidine
• Triamterene
• Vancomycin
• Phenytoin
• Beta blockers
• Calcium channel blockers
• Oral contraceptives
• Corticosteroids
• Diuretics
• Estrogens
• Phenothiazines
• Sympathomimetics
• Chromium
• Coenzyme Q10
• Garlic
• Green tea

A medical provider may have you stop taking metformin temporarily if you have an upcoming surgery or other radiology procedure since metformin can interact with contrast dyes and other medications used in these procedures.

When to See a Medical Provider

If you have type 2 diabetes that is not well-controlled, speak to your medical provider about medication that may help control your glucose levels.

If you take metformin and have questions or concerns about side effects, see a healthcare provider.

Before stopping metformin, make sure that your medical provider has outlined a plan to safely control glucose levels.

If you have questions about diabetes treatment, glucose control, or side effects, you can speak with a medical provider in the K Health app, right from the comfort of your home.