Metformin

What is metformin?

Metformin belongs to a class of drugs called biguanides. It is prescribed to help people with type 2 diabetes gain improved control over their blood sugar levels by decreasing the body’s absorption and production of glucose during digestion.¹

What You Need To Know About Type 2 Diabetes

Metformin, which can only be obtained with a doctor’s prescription, is available as an immediate-release tablet, an extended-release tablet, and an oral solution. The drug is sold in both generic and branded versions — brand names include Glucophage, Glumetza, Fortamet, and Riomet.

The immediate-release versions (both the tablet and the oral solution) are indicated by the US Food and Drug Administration (FDA) for improving glycemic control in both adults and children (ten years and older) with type 2 diabetes. The extended-release version is indicated exclusively for adults as it hasn’t been tested for safety and effectiveness in children.² ³

Doctors sometimes prescribe metformin off-label for type 2 diabetes prevention, gestational diabetes treatment, antipsychotic-induced weight gain management, and polycystic ovary syndrome (PCOS) treatment and prevention.⁴

How do you take metformin?

How you take metformin will depend on the form you were prescribed, the condition being treated, and your age. In most cases, doctors start by prescribing a low dose of the medication and slowly increase the amount until adequate glycemic control is achieved.

Drug forms and strengths

Metformin is available in three forms:

• Immediate-release tablets

• Immediate-release oral solution

• Extended-release tablets

Metformin immediate-release tablets are available in the following strengths:⁵

• 500mg

• 850mg

• 1,000mg

Metformin immediate-release oral solution is available in a single concentration:⁶

• 500mg/5mL

Finally, metformin extended-release tablets are available in the following strengths:⁷

• 500mg

• 750mg

• 1,000mg

Typical adult dosage

Adults taking the tablet form will usually take metformin twice daily with food. However, those taking higher doses (more than 2,000mg daily) may benefit from splitting their daily amount into three separate doses.

Doctors may increase the daily dose once every two weeks by 500mg or 850mg. The maximum recommended daily dose is 2,550mg.⁸

Those taking the oral solution will typically start with 5mL or 8.5mL (500mg or 850mg of metformin) once daily with food. The maximum daily dose (2,550mg) and the guidelines for dosage increases are the same as those for the tablet form; 500mg or 850mg increases once every two weeks as needed.⁹

When measuring the oral solution, it’s essential to use a specialized device for measuring medication. Household spoons are not accurate for dosing. If your medication didn’t come with a measuring device, such as a cup or dropper, ask your pharmacist for one. 

The extended-release tablet form of metformin is usually taken once daily with an evening meal. There is no precise dosing recommendation for people taking this form of metformin. Your doctor will consider your personal characteristics, including your age, condition, glucose control, and overall health, to determine the appropriate dose for you. The maximum recommended daily amount for the extended-release form is 2,000mg.¹⁰

The extended-release tablets are specially designed to deliver the medication gradually over time. Do not crush, chew, or split the tablets.

Typical pediatric dosage

Children may take metformin in either of its immediate-release forms. 

Children aged ten years and older who are taking the tablet form typically start with 500mg once daily with a meal. Doctors may increase the dose as needed by 500mg once weekly, up to a maximum daily dose of 2,000mg. Those on higher doses may take two smaller doses per day to improve tolerability.¹¹

Children aged ten years and older taking the oral solution usually start with 5mL twice daily with meals. Dosage may be increased by 5mL once weekly as determined by their doctor. The maximum recommended daily dose is 20mL (or 2,000mg).

The extended-release version of metformin has not been adequately tested in children, so pediatric dosing guidelines for this form are unavailable.

Take metformin precisely as prescribed by your doctor, even if your prescribed dose falls outside the typical range. Some personal characteristics may affect your body’s handling of the drug, and your doctor will consider these variations when determining the appropriate dose for you.

Seeing results

Metformin is typically taken long-term, and you may not see its effects on your blood sugar right away.

In a study comparing the immediate- and extended-release forms, researchers found that both types produced significant (and comparable) effects by 12 weeks. However, there was evidence of the drug’s effectiveness in both groups within one week.¹²

If you’re taking metformin and your blood sugar levels aren’t stabilizing, your doctor can help you adjust the dose, add another drug, or switch to a different type of medication. Do not increase your dose or stop taking metformin without guidance from your doctor.

Warnings and potential side effects of metformin

Metformin has a US FDA boxed warning. There have been cases where people taking metformin have developed a severe and life-threatening condition called lactic acidosis, which is characterized by increased blood lactate concentrations, an increased lactate: pyruvate ratio, and anion gap acidosis. This adverse effect requires hospitalization, and its early signs may be subtle. It’s essential to stay vigilant in monitoring for the symptoms of lactic acidosis, which may include any of the following:¹³

• Malaise

• Drowsiness

• Muscle aches and pains

• Cold feeling in the arms and legs

• Abdominal pain

• Trouble breathing

• Slow or irregular heartbeat

Anyone taking metformin can develop lactic acidosis, but the risk is highest among certain groups, particularly:

• People with kidney or liver disease

• Those taking drugs that impair renal function, interfere with acid-base balance, trigger significant hemodynamic changes, or increase metformin accumulation in the body

• People aged 65 years or older

• Those taking intravascular iodinated contrast agents for radiologic testing requiring contrast

• People who have restricted food and liquid intake or who are fasting in relation to a surgical or other procedure (including lab testing)

• People who get dehydrated, either from vomiting and diarrhea or excessive sweating

• Individuals experiencing a cardiovascular event triggering low oxygen levels (including acute congestive heart failure)

• Patients with a heart attack, stroke, or sepsis

• Those who drink alcohol excessively

If you experience any symptoms of lactic acidosis, stop taking metformin and seek urgent medical care.

Metformin has known side effects. Typically, these adverse effects are mild and temporary. If you have severe or persistent side effects, speak with your doctor.

Mild side effects associated with metformin include the following:¹⁴

• Bloating

• Stomach pain

• Nausea, vomiting

• Diarrhea

• Indigestion, heartburn

• Gas

• Constipation

• Metallic taste in the mouth

• Headache

• Flushing

• Muscle pain

• Changes in nail health or appearance

• Lack of energy

• Decreased appetite

• Rash

Severe side effects requiring medical attention include the signs of lactic acidosis outlined above and the following:¹⁵

• Symptoms of hypoglycemia, which may include:¹⁶

  • Dizziness

  • Confusion

  • Shakiness

  • Weakness

  • Difficulty speaking

  • Feeling anxious or jittery

  • Fast heart rate

• Symptoms and signs of low vitamin B12 levels, which may include:¹⁷

  • Poor balance

  • Numbness in the arms and legs

  • Tingling in the arms and legs

  • Weakness

  • Anemia

Severe side effects are typically treatable when caught early, but you must consult your doctor as soon as possible for guidance.

Who should not take metformin?

The groups outlined above who are at risk for developing lactic acidosis must inform their doctor of their risk factors before starting metformin. Additionally, the drug is contraindicated in the following groups:¹⁸

• People with severe kidney or liver impairment

• Those with known sensitivity to metformin

• People with acute or chronic metabolic acidosis, including diabetic ketoacidosis

• People with acute or chronic low oxygen levels

• Patients with dehydration, sepsis, or those undergoing surgery

• Patients that will be undergoing testing requiring an injection of dye or contrast

• People with known type 1 diabetes

Long-term use of metformin

Metformin is typically well-tolerated and suitable for long-term use. However, there are associations between long-term metformin and an increased risk of vitamin B12 deficiency. Therefore, if you’re taking metformin for a long period, your doctor may advise routine B12 testing and supplementation.¹⁹

Missed doses

If you miss a dose of metformin, take it as soon as you remember unless it’s nearly time for your next dose. If that’s the case, skip the missed dose and resume your usual schedule. Do not double your dose to make up for a missed one, as this may increase the risk of severe adverse side effects, including hypoglycemia.²⁰

Overdoses

A metformin overdose may trigger hypoglycemia or lactic acidosis. If you think you may have taken too much medication, seek urgent medical attention. In some cases, doctors recommend hemodialysis to clear excess metformin from the body.²¹

Signs of a metformin overdose may include any symptoms of hypoglycemia or lactic acidosis (see Warnings and potential side effects) and the following:²²

• Weakness

• Extreme tiredness

• Nausea, vomiting

• Stomach pain

• Poor appetite

• Shortness of breath or deep, rapid breathing

• Abnormally fast or slow heartbeat

• Dizziness, lightheadedness, or feeling faint

• Feeling cold

• Flushing

• Muscle pain

What to discuss with your doctor before you start taking metformin

Metformin is available by prescription only, so you’ll need to meet with your doctor before you start taking it. At your appointment, you should discuss the following topics:

• Let your doctor know about all allergies you have and any allergic reactions to medications you’ve experienced.

• Bring a list of all medications, supplements, and herbs you’re taking, even if you only take them occasionally.

• Tell your doctor about any existing or suspected medical conditions, especially those that increase your risk of lactic acidosis (see Warnings and potential side effects).

• Let your doctor know if you are pregnant, planning to become pregnant, or breastfeeding.

Stopping metformin

Do not stop taking metformin without consulting your doctor. While there are some situations where you may need to stop taking metformin temporarily, such as during bouts of illness that may cause dehydration, you should not stop taking the drug without guidance from your prescriber. However, if you develop signs and symptoms of lactic acidosis, discontinue the medication and seek immediate medical attention.²³

Metformin in pregnancy and breastfeeding

The US FDA designated metformin as a pregnancy category B drug.²⁴

Evidence suggests that metformin is typically well-tolerated in pregnancy and does not increase the risk of congenital abnormalities. If a patient develops gestational diabetes mellitus during pregnancy, their doctor may recommend metformin if they cannot achieve target glucose levels through dietary measures. However, this is an off-label use for which the drug is not indicated by the US FDA.²⁵

In a study of long-term outcomes associated with metformin use during pregnancy, researchers found no increased long-term risk associated with metformin or combination treatment (metformin and insulin) compared to insulin alone. However, extra caution and monitoring may be necessary in cases where there’s a risk of fetal undernutrition.

Further, metformin may reduce the risk of certain pregnancy-related conditions, including gestational weight gain in the pregnant patient, which, if excessive, can lead to complications. Notably, though, pregnant patients taking metformin are significantly more likely to experience adverse gastrointestinal effects.²⁶

Studies in animals indicate that metformin passes through breast milk. There are no adequate studies in humans to determine its effect on the infant or the mother’s milk production. It’s important to discuss the risks and benefits in your case with your doctor.²⁷

Interactions with other drugs

Metformin is known to interact with certain medications and substances, including the following:²⁸ ²⁹

Drugs interfering with the body’s elimination of metformin

Medications that affect transport systems in the kidneys may slow the body’s elimination of metformin, increasing exposure to the drug and the risk of lactic acidosis. These drugs include ranolazine (Ranexa), vandetanib (Caprelsa), dolutegravir (Tivicay, Dovato), and cimetidine (Tagamet).

Carbonic anhydrase inhibitors

Drugs such as topiramate (Topamax), zonisamide (Zonegran), acetazolamide (Diamox), and dichlorphenamide (Keveyis), which trigger a decline in blood levels of bicarbonate, may increase the risk of lactic acidosis when taken alongside metformin.

Drugs affecting glycemic control

Drugs known to induce hyperglycemia or hypoglycemia may influence the effectiveness of metformin. These drugs include diuretics, corticosteroids, phenothiazines, sympathomimetics, calcium channel blockers, thyroid drugs, estrogens, oral contraceptives, isoniazid, nicotinic acid, and phenytoin (Dilantin).

Insulin secretagogues or insulin

People taking metformin with insulin or insulin secretagogues, such as a sulfonylurea medication (Diabinese, Glynase), face a higher risk of hypoglycemia, and doses should be adjusted accordingly.

Alcohol

Alcohol increases the effect of metformin on lactate metabolism, increasing the risk of lactic acidosis.

Allergy information

Metformin allergies are unusual and typically result in the development of a rash or skin lesions.³⁰

Very rarely, a person may experience the following signs of a drug allergy while taking metformin:

• Swelling under the skin

• Swelling of the mouth, tongue, or throat

• Vomiting

• Difficulty breathing

• Fast heartbeat

• Loss of consciousness

If you think you may be allergic to metformin, seek immediate medical attention. Your doctor will likely recommend switching to a different therapy.

Drug approval history³¹

1994: The US FDA approves metformin in its immediate-release form

2000: The US FDA approves the extended-release version of metformin

Tips and advice for taking metformin

The following tips can help you maximize the effectiveness and safety of metformin.³² ³³

• Take metformin with a meal.

• Swallow the tablets whole.

• You may pass a soft mass in your stool that looks like a metformin tablet — this is normal and nothing to worry about.

• Stressful situations, such as illness and injury, may change your body’s handling of glucose and metformin, and you may need dosage adjustments (guided by your prescriber).

• Check your blood sugar regularly as directed by your doctor.

• Metformin may induce ovulation in some premenopausal women who haven’t ovulated for some time; speak with your doctor about preventing unintended pregnancies. 

• Minimize your alcohol intake while on metformin and avoid binge drinking.

• Store your tablets between 68° and 77°F (20° and 25°C) and solution between 59° and 86°F (15° and 30°C).

• Adhere to your prescribed diet and exercise plan — metformin is not a substitute for a healthy, diabetes-friendly diet and lifestyle.