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Metformin: What is it and How Does it Work?

Metformin: What is it and How Does it Work?

The American Diabetes Association estimates that approximately 34.2 million Americans currently suffer from diabetes. Of that number, roughly 31 million of these patients have Type 2 diabetes. Type 1 diabetes, often called juvenile diabetes, is a condition in which patients do not produce enough insulin to meet their body’s needs, while Type 2 diabetes is often associated with lifestyle factors and is characterized by insulin resistance. When patients experience insulin resistance, their bodies do not respond to insulin as they should. Although the first step in treating Type 2 diabetes is often lifestyle changes, such as losing weight, eating a healthy diet, and getting more exercise, some people are not able to manage their condition with lifestyle changes alone. In these patients, prescription medications like metformin may be prescribed in conjunction with lifestyle changes in order to bring the patient’s diabetes under control. Prescription medications for Type 2 diabetes include injectable insulin and oral diabetes medications like metformin. 

What is metformin?

Metformin is a prescription medication that belongs to a class of drugs called biguanides. The drug is primarily used for the treatment of Type 2 diabetes and is the most popular medication for the treatment of Type 2 diabetes worldwide, having been prescribed to over 120 million people. Metformin is the only biguanide used to treat diabetes; most other biguanides that remain on the market are used to treat malaria.  The U.S. Food and Drug Administration approved metformin for use in the United States in 1995. Today, metformin 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?

Metformin is used for the treatment of Type 2 diabetes. Approximately ten percent of Americans have some form of diabetes. Of the people who have been diagnosed with one of the two forms of diabetes, about 90 percent of people have Type 2 diabetes.  While Type 1 diabetes is characterized by the body’s inability to produce enough insulin, Type 2 diabetes is defined by the body’s resistance to the insulin that it produces. People with both Type 1 and Type 2 diabetes are unable to properly process the sugar, or glucose, in the food we eat in order to turn it into energy. The body breaks down food into glucose and releases it into the bloodstream after we finish eating. As glucose enters the bloodstream, it causes blood sugar levels to rise, which triggers the release of insulin by the pancreas; insulin is a hormone that tells the body to start using the sugar in the blood for energy.  People with Type 2 diabetes are resistant to insulin, which means that levels of blood sugar in the body stay high for longer than they are supposed to. Metformin is used to treat Type 2 diabetes because it works by increasing the body’s sensitivity to insulin and directs it to respond to the hormone. Patients who are unable to control their blood sugar through lifestyle changes or medications like metformin can experience dangerous health effects and complications. Serious conditions and complications associated with prolonged high blood sugar include:

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

How does metformin work?

Metformin works by influencing the amount of sugar, or glucose, in the blood. Specifically, metformin works by decreasing the liver’s production of glucose, increasing target cell insulin sensitivity, and reducing the absorption of glucose by the gastrointestinal tract. Metformin does not act on the production of insulin or influence the production of insulin in any way; it works by increasing the body’s sensitivity to insulin. When a person is more sensitive to insulin,  the body can convert glucose in the blood to energy, which in turn causes the liver to decrease production of glucose and regulates blood sugar levels. 

What side effects are associated with metformin?

Metformin is the most commonly prescribed medication for Type 2 diabetes in the world. Although the medication is intended for long-term use, it is associated with numerous side effects. The long list of side effects associated with metformin are the reason why one study determined that metformin has the lowest adherence rate of Type 2 diabetes medications. Although there are many side effects associated with metformin, some of which are serious, the medication has fewer side effects than other Type 2 diabetes and prediabetes medications. Fortunately, 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:

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

Patients taking metformin who experience side effects while taking metformin are most likely to experience diarrhea, nausea, and vomiting. Side effects are most likely to occur when a patient first starts taking metformin or their dose of the medication is increased. As the body adjusts to metformin, many people find that their side effects are reduced or disappear entirely. Metformin is available in both an extended release and immediate release version of the medication, and the immediate release version of the drug is more likely to cause side effects. Patients can reduce their risk of experiencing side effects by taking the medication with a meal to slow absorption or by taking the extended release form of the drug.

Most people are likely to experience common side effects that do not require medical attention, but some side effects associated with metformin are more serious and require the attention of a medical professional immediately. These side effects are rare but have occurred on occasion. The most serious side effects caused by metformin are lactic acidosis, anemia (low levels of iron in the blood), and hypoglycemia (low blood sugar).

Lactic acidosis is a pH imbalance in the body that occurs when people overproduce or underuse lactic acid. If left untreated, lactic acidosis can be fatal, but this serious condition can be treated if caught early. It is believed that metformin can contribute to lactic acidosis when the medication builds up in the blood over time. Symptoms of lactic acidosis include:

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

Some patients are more likely to experience lactic acidosis when taking metformin than other patients. Risk factors associated with an increased likelihood of lactic acidosis include excessive alcohol use, liver problems, heart problems like acute heart failure, kidney disease or kidney problems, recent heart attack, and surgery or radiology procedures that use iodine contrast. 

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://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