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Metformin Side Effects: What are They, and How to Manage Them

An estimated 34.2 million Americans have diabetes according to the American Diabetes Association, and of that 34.2 million, about 31 million people are diagnosed with Type 2 diabetes, which is characterized by insulin resistance. While healthy lifestyle changes is the first “prescription” most patients with Type 2 diabetes receive from their doctors, eating a healthy diet and getting more exercise is not always enough for patients to keep their diabetes under control. In these cases, injectable insulin or oral diabetes medications like metformin may be prescribed. Metformin is a long-term medication taken for the management of Type 2 diabetes, and because some patients may take it for many years, side effects are a concern. Metformin side effects can include both mild and serious symptoms. 

Overview

Metformin hcl is part of a class of drugs called biguanides, and it is the most popular drug for the treatment of Type 2 diabetes on the market, having been prescribed to over 120 million people around the world. However, because it is the only biguanide available for the treatment of Type 2 diabetes in many countries, it is almost in a class of its own. Although there are some biguanides on the market for the treatment of malaria, most diabetes medications have been removed from the market. Biguanides like metformin work by controlling the amount of sugar in your blood. Insulin production is not affected by metformin, but sensitivity to insulin is increased when the drug is used. As insulin sensitivity increases, the body is better able to use the glucose, or sugar, in the blood as energy, which in turn reduces the amount of glucose produced by the liver and regulates blood sugar levels. Metformin is sold under the brand names Glucophage, Glucophage XR, Glumetza, Riomet, Fortamet, and a few more, and is available in both instant release tablets and extended-release formulas.

Conditions Treated

More than ten percent of Americans have diabetes, and of that number, about 90 percent are diagnosed with Type 2 diabetes, i.e. Type 2 diabetes mellitus, which is characterized by insulin resistance rather than inability to produce insulin like in Type 1 diabetes. In both types of diabetes, patients have difficulty processing the sugar we consume into energy for the body. After eating, the body begins to break down food into glucose, which is then released into the bloodstream. As the levels of sugar in the bloodstream rise, our blood sugar level increases. A hormone called insulin is then released by the pancreas; insulin directs the body to use the sugar in your blood for energy. However, patients with Type 2 diabetes cannot use insulin properly, while those with Type 1 diabetes either cannot produce insulin or don't make enough of it. Metformin is used for the treatment of Type 2 diabetes and works by increasing insulin sensitivity, directing our bodies to respond to the hormone when it is released by the pancreas. Without medications like metformin, people with Type 2 diabetes have uncontrolled high blood sugar (also known as hyperglycemia), which can cause dangerous health effects. 

Serious conditions and complications associated with high blood glucose include:

  • Increased risk of kidney disease

  • Increased risk of heart problems like heart failure and heart attack

  • Nerve damage in the feet and hands (neuropathy)

  • Damage to the blood vessels of the eyes (retinopathy)

Another common indication for metformin aside from type 2 diabetes mellitus and approved by the Food and Drug Administration (FDA) is to help women with polycystic ovary syndrome, also known as PCOS. One symptom of polycystic ovary syndrome is high insulin, which can be controlled with a metformin regimen, also helping to reduce the risk of women with PCOS from also  developing type 2 diabetes mellitus, especially if the PCOS has already put them into prediabetes. Additionally, weight gain caused by other PCOS factors can also be counteracted my metformin. 

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Metformin Side Effects

Metformin is intended to be taken long-term for the management of Type 2 diabetes, so naturally, many patients are concerned about the drug’s common side effects. It should be noted although the side effects of metformin are lesser than other medications for Type 2 diabetes, some of the side effects of metformin can be serious. One study found that as a result of its side effects, metformin had the lowest adherence rate of diabetes medications that were studied. Nonetheless, there are ways to reduce the number and severity of the side effects of metformin. 

Common side effects of metformin that usually do not require medical attention include:

  • Diarrhea

  • Bloating

  • Stomach pain

  • Heartburn

  • Nausea or vomiting

  • Gas

  • Constipation

  • Headache

  • Weight loss

  • Unpleasant metallic taste in the mouth

Diarrhea is the most commonly experienced side effect of metformin, while nausea and vomiting are also common. Most patients find that their side effects go away after their body begins to adjust to the medication, but any side effects that become intolerable or are prolonged should always be brought to the attention of your healthcare provider. Some side effects of metformin can be avoided by taking the medication with a meal or by taking the extended-release tablet, rather than the immediate release tablet version of the drug. 

Other side effects associated with metformin are more serious and require medical attention immediately. These side effects are rare but have occurred in patients taking metformin. The most serious side effects associated with metformin are lactic acidosis, anemia, and hypoglycemia.

Lactic acidosis is a medical condition in which people overproduce or underuse lactic acid, causing an imbalance of the pH of the body. Although it can often be treated, lactic acidosis can be fatal if left untreated. Metformin can contribute to risk of lactic acidosis if it builds up in the blood. Symptoms of lactic acidosis include:

  • Weakness

  • Nausea

  • Trouble breathing

  • Lightheadedness

  • Feeling cold

  • Flushing or sudden reddening and warmth of the skin

  • Extreme fatigue

  • Decreased appetite

  • Vomiting

  • Dizziness

  • Fast or slow heart rate

  • Muscle pain

  • Stomach pain with any of these symptoms

Several risk factors increase the likelihood that a patient will experience lactic acidosis while taking metformin. These risk factors include kidney disease or kidney problems, heart problems including acute heart failure or recent heart attack, liver disease, excessive alcohol use, and surgery or radiology procedures that use iodine contrast. 

Drug interactions are not generally a concern for those taking metformin, though a study did find that cimetidine, an OTC heartburn medication, can increase the risk of lactic acidosis as a side effect of metformin. However, as always, it's important to disclose any other medications you're taking with your healthcare professional whenever they are about to prescribe a new medication to ensure they can provide the most accurate medical advice possible. 

Anemia is a condition characterized by low levels of red blood cells in the body. Metformin can contribute to anemia by reducing the levels of vitamin B-12 in the body, which can occasionally cause anemia. Common symptoms of anemia and vitamin b12 deficiency include:

  • Tiredness

  • Lightheadedness

  • Dizziness

Hypoglycemia, or low blood sugar, is not caused by metformin alone, but the drug can contribute to hypoglycemia in patients who have a poor diet, drink alcohol excessively, exercise strenuously, or take other diabetes medications. Symptoms of hypoglycemia include:

  • Weakness

  • Nausea

  • Stomach pain

  • Lightheadedness

  • Tiredness

  • Vomiting

  • Dizziness

  • Abnormally fast or slow heartbeat

Sources:

https://www.healthline.com/health/diabetes/metformin-side-effects 

https://www.healthline.com/health-news/why-so-many-people-with-diabetes-stop-taking-metformin 

https://www.cdc.gov/diabetes/basics/type2.html 

https://www.cdc.gov/diabetes/basics/diabetes.html 

https://www.diabetes.org/resources/statistics/statistics-about-diabetes 

https://medlineplus.gov/druginfo/meds/a696005.html 

https://www.verywellhealth.com/biguanides-diabetes-medications-1087355 

https://www.tandfonline.com/doi/full/10.3109/10717544.2015.1089957 

https://dom-pubs.onlinelibrary.wiley.com/doi/abs/10.1111/dom.13160

https://spectrum.diabetesjournals.org/content/19/4/202#:~:text=Procainamide%2C%20digoxin%2C%20quinidine%2C%20trimethoprim,%2C27%20(Table%201) 

Published July 31st, 2020 by Bridget Reed
Fact Checked by Chris Riley

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