What is Metformin?

Approximately 31 million of the estimated 34.2 million of Americans with diabetes suffer from Type 2 diabetes mellitus, according to DPP and the American Diabetes Association.

This common, but serious, health condition is characterized by insulin resistance, a condition in which the body does not properly respond to the release of insulin after meals, which can often lead to dangerously high blood glucose levels, known as high blood sugar. 

Unlike Type 1 diabetes, which is characterized by insufficient quantities of insulin, patients with Type 2 diabetes can sometimes manage their condition by living a healthy lifestyle, as eating a healthy diet and getting more exercise, among other habits, can go a long way towards fighting Type 2 diabetes, as well as diabetes prevention for those who are only in the prediabetes stage.

Other patients require medication in addition to lifestyle changes in order to keep their Type 2 diabetes under control.

Prescription medications for Type 2 diabetes often include injectable insulin and oral diabetes medications like metformin. So, what is metformin?

What is metformin?

A routine prescription drug for more than 120 million people around the world, metformin is the most popular drug for Type 2 diabetes care.

Metformin belongs to a class of medications called biguanides, which are used for Type 2 diabetes as well as other illnesses, like malaria.

In many countries, other biguanides have been taken off the market, and metformin is the only biguanide available for the treatment of Type 2 diabetes.

The U.S. Food and Drug Administration (FDA) first approved metformin for use in the United States in 1995.

The medication is sold under the brand names Glucophage and Glucophage XR and is available in both immediate and extended-release formulas.  

What conditions are treated with metformin?

Diabetes is extremely common in the United States, with more than ten percent of the American population diagnosed with diabetes.

Approximately 90 percent of those who are diagnosed have Type 2 diabetes, which is characterized by insulin resistance.

Unlike Type 1 diabetes, which is sometimes called juvenile diabetes, Type 2 diabetes is a condition in which the body does not respond to insulin in the normal manner. 

No matter which type of diabetes a person has, they struggle to properly use the sugar, or glucose, from the food they consume and process it as energy. In people without diabetes, the body begins to break down our food into glucose after we finish eating.

Glucose is then released into the bloodstream, which causes our blood sugar levels to rise.

The body then directs the pancreas to produce a hormone called insulin when it detects a rise in blood sugar levels; insulin directs the body to use the sugar in your blood for energy. 

Diabetics either do not have enough insulin, as is the case with Type 1 diabetes, or cannot use it properly due to insulin resistance, which occurs in Type 2 diabetes, so they are unable to use the sugar in the bloodstream properly. 

As a result, blood sugar levels remain higher than they should.

Type 1 diabetes and gestational diabetes require injections of insulin to help the body use glucose, while metformin is used to treat Type 2 diabetes.

If diabetes is left untreated through either medication or lifestyle changes, patients will have elevated blood sugar levels for a prolonged period of time, which can cause dangerous medical conditions.

Another common condition for which metformin is prescribed is polycystic ovary syndrome (PCOS), which puts people at higher risk of developing diabetes as this condition can also affect insulin function. Serious conditions and complications associated with high blood glucose include:

• Increased risk of heart problems like heart disease
• Increased risk of kidney disease
• Nerve damage in the feet and hands (neuropathy)
• Damage to the blood vessels of the eyes (retinopathy)

How does metformin work?

Metformin is a biguanide, and like other medications in its class, it works by controlling the amount of sugar, or glucose, in your blood.

Specifically, metformin works to decrease absorption of glucose by the gastrointestinal tract, reduce glucose production by the liver, and increase target cell insulin sensitivity. 

Insulin production is not affected by metformin; the drug works by increasing the body’s response to even low levels of insulin.

When the body is sufficiently sensitive to insulin, it is able to properly convert glucose to energy.

This results in a lower amount of glucose being produced by the liver and helps to regulate blood sugar levels. 

What side effects are associated with metformin?

Metformin is intended for long-term use and is the most frequently prescribed Type 2 diabetes medication in the world, but it is not without side effects.

Like other Type 2 diabetes and prediabetes medications, metformin is associated with a long list of side effects, some of which are serious. 

However, the medication has a shorter list of side effects than other medications in its class.

The long list of side effects contributes to metformin having the lowest adherence rate of a group of diabetes medications examined in one study.

However, it is possible to reduce the number and severity of side effects experienced while taking metformin.

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

• Diarrhea
• Bloating not from weight gain
• Gas
• Weight loss
• Constipation
• Stomach pain
• Heartburn
• Headache
• Nausea or vomiting
• Unpleasant metallic taste in the mouth

Diarrhea, nausea, and vomiting, respectively, are the most commonly experienced side effects of metformin.

As patients’ bodies adjust to the medication, most side effects subside and eventually disappear, but some patients find the side effects intolerable.

Patients taking the immediate-release version of the medication have been found to experience a higher likelihood of side effects than those who take the extended-release version of metformin; taking the medication with a meal also reduces the likelihood of experiencing side effects. 

While most side effects caused by metformin are mild and do not require medical attention, some can be serious.

Serious side effects caused by metformin are rare but have occurred on occasion. The most serious side effects associated with metformin are lactic acidosis, hypoglycemia, and anemia.

Lactic acidosis is a condition that occurs when people either overproduce or underuse lactic acid, creating a pH imbalance in the body. Lactic acidosis can be fatal if left untreated, but when detected early, it is treatable.

Metformin contributes to a risk of lactic acidosis because it can build up in the blood. Symptoms of lactic acidosis include:

• Feeling cold
• Weakness
• Decreased appetite
• Stomach pain with any of these symptoms
• Muscle pain
• Flushing or sudden reddening and warmth of the skin
• Nausea
• Fast or slow heart rate
• Vomiting
• Dizziness
• Extreme fatigue
• Trouble breathing
• Lightheadedness

Some patients are more at risk of experiencing lactic acidosis than others while taking metformin.

Risk factors associated with an increased likelihood of lactic acidosis include excessive alcohol use, liver problems, kidney disease or kidney problems, heart problems including acute heart failure, recent heart attack, and surgery or radiology procedures that use iodine contrast. 

Anemia, a medical condition characterized by low red blood cell levels in the body, can sometimes be caused by metformin; the medication has been known to reduce the level of vitamin B-12 in the body, which can contribute to anemia.

Common symptoms of anemia include:

• Dizziness
• Lightheadedness
• Tiredness

Patients who drink alcohol to excess, take other diabetes medications, have a poor diet, or exercise strenuously may experience hypoglycemia, or low blood sugar, when taking metformin. Symptoms of hypoglycemia include:

• Weakness
• Nausea
• Stomach pain
• Lightheadedness
• Tiredness
• Vomiting
• Dizziness
• Abnormally fast or slow heartbeat

Are there any drug interactions associated with metformin?

When taken with metformin, certain medications may increase your risk of developing lactic acidosis. Lactic acidosis is a serious side effect of metformin that can be potentially fatal, so tell your doctor if you are taking any of the following types of medications before taking metformin :

• Oral contraceptives
• Corticosteroids, including prednisone
• Diuretics, such as acetazolamide
• Blood pressure medication, including amlodipine/Norvasc
• Anticonvulsants, including topiramate (Topamax) and zonisamide (Zonegran)
• Antipsychotic drugs, including chlorpromazine

Are there any risks associated with metformin?

Although metformin is an extremely popular medication for the treatment of diabetes, it’s not right for everyone.

Depending on the existing medical conditions a patient may have, some individuals may not be able to tolerate metformin or may be at a higher risk of certain serious side effects due to their medical history.

If you have a history of any of the following medical conditions, it’s very important that you speak to your doctor about your medical history and discuss the drug information prior to starting a metformin regimen:

• Metabolic acidosis without coma
• Abnormal creatinine clearance due to septicemia, shock, myocardial infarction or lactation
• Severe liver disease or disrupted kidney function
• Diabetic ketoacidosis
• Hypersensitivity
• Congestive heart failure
• Metabolic acidosis with coma

References:

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://www.healthline.com/health/grapefruit-and-metformin

https://www.rxlist.com/consumer_metformin/drugs-condition.htm

https://www.rxlist.com/consumer_metformin/drugs-condition.htm#what_are_warnings_and_precautions_for_metformin

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Diabetic.org is devoted to producing expert and accurate articles and information for our readers by hiring experts, journalists, medical professionals, and our growing Diabetic.org community. We encourage you to read more about our content, editing, and fact checking methods here. This was fact checked by Erik Rivera and medically reviewed by Dr. Angel Rivera.