How Does Metformin Work?

Published August 1st, 2020 by Bridget Reed
Fact Checked by
Erik Rivera
Medically Reviewed:
Dr. Angel Rivera
Updated Date: Jul 13th, 2021

Of the estimated 34.2 million Americans with diabetes, approximately 31 million people suffer from Type 2 diabetes according to DPP and the American Diabetes Association. Unlike Type 1 diabetes, in which people do not produce enough insulin, Type 2 diabetes is characterized by insulin resistance, a condition in which the body does not respond to the release of insulin as it normally should. Patients with Type 2 diabetes are often given a “prescription” of a healthy lifestyle when first diagnosed by their doctors, because eating a healthy diet and getting more exercise, among other habits, are important steps towards controlling Type 2 diabetes. However, for some patients, lifestyle changes alone are not enough for patients to keep their diabetes under control. Generally speaking, prescription medications for Type 2 diabetes include injectable insulin and oral diabetes medications like metformin. Metformin is one of the most popular and well studied drugs for the treatment of Type 2 diabetes, and many patients take it for years despite the long list of side effects associated with the medication. If you are considering taking metformin to control your Type 2 diabetes, you may be wondering “how does metformin work?” 

What is metformin?

Metformin has been prescribed to over 120 million people around the world for the diabetes treatment of Type 2 diabetes, making it the most popular Type 2 diabetes drug in the world. The medication is part of a class of drugs called biguanides, but in many countries, it is the only biguanide available for the treatment of Type 2 diabetes. Some biguanides remain on the market for the treatment of malaria, but the majority of diabetes medications have been removed from the market. Metformin was first approved for use in the United States in 1995 by the U.S. Food and Drug Administration (FDA) and 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?

Over ten percent of the American population is diagnosed with diabetes, and of that number, about 90 percent have Type 2 diabetes. Unlike Type 1 diabetes, which is characterized by reduced insulin production, Type 2 diabetes is characterized by insulin resistance; namely, the body does not respond to insulin in the normal manner. Regardless of which type of diabetes they are diagnosed with, people with diabetes struggle to use the sugar, or glucose, from the food they consume and process it as energy.  Normally, our bodies begin to break down the food we eat after we finish eating. Food is broken down into glucose,  which is then released into the bloodstream. The release of glucose, a type of sugar, into the bloodstream causes our blood sugar levels to rise. As the body detects a rise in blood sugar levels, a hormone called insulin is then released by the pancreas, which directs the body to use the sugar in your blood for energy. In normal people, the body begins to use the sugar in the blood for energy, but diabetics either cannot use insulin properly due to insulin resistance (Type 2 diabetes) or do not have enough insulin, which means that blood sugar levels remain higher than they should. People with Type 1 diabetes or gestational diabetes need injections of insulin to help their bodies utilize glucose, but metformin works by increasing insulin sensitivity and telling our bodies to respond to the hormone when it is released.  Patients who do not use insulin or metformin and cannot get a grip on their blood glucose control or blood glucose levels with lifestyle changes will have elevated blood sugar levels for an extended period of time, causing dangerous health effects and long term diabetes care. Serious conditions and complications associated with high blood glucose include:

  • Increased risk of kidney disease

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

  • Increased risk of heart problems like heart disease

  • Nerve damage in the feet and hands (neuropathy)

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How does Metformin Hcl work?

Biguanides like metformin work by controlling the amount of sugar, or glucose, in your blood. Specifically, metformin works to reduce production of glucose by the liver, decrease absorption of glucose by the gastrointestinal tract, and increase target cell insulin sensitivity. Metformin does not influence the production of insulin; it simply increases the body’s sensitivity to the hormone.  As insulin sensitivity increases, the body is able to properly convert the glucose to energy, which in turn reduces the amount of glucose produced by the liver and regulates blood sugar levels. 

What side effects are associated with metformin?

Although metformin is the most popular Type 2 diabetes medication in the world and is intended for long-term use, it is associated with numerous side effects. While the side effects list is lengthy and includes some serious side effects, metformin is associated with fewer side effects than other medications for Type 2 diabetes and even prediabetes. Due to the long list of side effects, metformin has the lowest adherence rate of a group of diabetes medications examined in one study. Nonetheless, there are ways 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

  • Heartburn

  • Diarrhea

  • Bloating not from weight gain

  • Constipation

  • Headache

  • Nausea or vomiting

  • Gas

  • Weight loss

  • Unpleasant metallic taste in the mouth

The most commonly experienced side effect of metformin is diarrhea, followed by nausea and vomiting. Most people notice that their side effects are reduced and eventually eliminated as their bodies adjust to the medication. Incidence of side effects are also higher with the immediate release version of the drug, so some side effects can be mitigated by taking the medication with a meal to slow absorption or by taking the extended release.  

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

When people overproduce or underuse lactic acid, a pH imbalance in the body called lactic acidosis occurs. Lactic acidosis is a serious condition that is fatal if left untreated, but can be treated if caught early enough. Metformin can build up in the blood, contributing to lactic acidosis in some people. Symptoms of lactic acidosis include:

  • Trouble breathing

  • Lightheadedness

  • Feeling cold

  • Weakness

  • Nausea

  • Fast or slow heart rate

  • Muscle pain

  • Flushing or sudden reddening and warmth of the skin

  • Vomiting

  • Dizziness

  • Extreme fatigue

  • Decreased appetite

  • Stomach pain with any of these symptoms

Certain risk factors are associated with an increased likelihood that a patient will experience lactic acidosis while taking metformin. Risk factors associated with an increased likelihood of lactic acidosis include heart problems including acute heart failure, kidney disease or kidney problems, recent heart attack, excessive alcohol use, liver problems and surgery or radiology procedures that use iodine contrast. 

Anemia is a medical condition characterized by low red blood cell levels in the body. Metformin sometimes reduces the level of vitamin B-12 in the body, which can contribute to anemia. Common symptoms of anemia include:

  • Dizziness

  • Tiredness

  • Lightheadedness

Hypoglycemia, or low blood sugar, can sometimes be caused when metformin is taken by patients who drink alcohol to excess, have a poor diet, take other diabetes medications, or exercise strenuously. Symptoms of hypoglycemia include:

  • Stomach pain

  • Lightheadedness

  • Weakness

  • Nausea

  • Dizziness

  • Abnormally fast or slow heartbeat

  • Tiredness

  • Vomiting

Are there any drug interactions associated with metformin?

Taking certain medications with metformin can increase your risk of developing lactic acidosis, a serious side effect that can be potentially fatal. Before taking metformin, tell your doctor if you are taking any of the following types of medications:

  • Diuretics, such as acetazolamide

  • Blood pressure medication, including amlodipine/Norvasc

  • Oral contraceptives

  • Corticosteroids, including prednisone

  • Anticonvulsants, including topiramate (Topamax) and zonisamide (Zonegran)

  • Antipsychotic drugs, including chlorpromazine

Are there any risks associated with metformin?

Metformin is a highly popular diabetes medication, but it is not appropriate for use by all patients. Some patients may not be able to tolerate metformin based on existing medical conditions or may be at higher risk of certain serious side effects due to their medical history. Patients with a history of any of the following medical conditions should speak to their doctors prior to starting a metformin regimen:

  • Hypersensitivity

  • Metabolic acidosis with coma

  • Metabolic acidosis without coma

  • Severe renal disease or kidney failure

  • Chronic heart failure

  • Diabetic ketoacidosis

  • Abnormal creatinine clearance due to septicemia, shock, myocardial infarction or lactation



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