Metformin hydrochloride is a medication used in conjunction with diet modification, weight loss, and exercise to treat Type 2 diabetes mellitus. Metformin is considered a first-line medication to safely and effectively lower blood glucose levels. Metformin is in the class of medications called biguanides. These medications help with hyperglycemia (elevated blood glucose) by reducing the production of glucose in the liver and promoting the uptake of excess glucose by skeletal muscle.
Metformin is widely available as a generic medication or under the brand names listed below.
Metformin is also available as a combination medication with other classes of diabetes medications such as sulfonylureas, DPP-4 inhibitors, or sodium-glucose cotransporter 2 (SGLT2) inhibitors.
Metformin is available in the dosage forms and strengths listed below.
Tablet: 500 mg, 850 mg, 1000 mg
Liquid solution: 500 mg per 5 ml
Extended-release tablet: 500 mg, 750 mg, 1000 mg
Extended-release liquid suspension: 500 mg per 5 ml
Metformin has been approved by the Food and Drug Administration (FDA) for use in adults and children older than 10 years of age for the treatment of Type 2 diabetes and polycystic ovary syndrome (PCOS). Metformin is also used off-label for the prevention of diabetes onset in individuals with prediabetes who have an increased risk for developing Type 2 diabetes. Metformin should not be used in the management of Type 1 diabetes mellitus. Metformin may be used with caution in certain individuals with kidney disease. Individuals with liver disease should avoid metformin use.
Metformin dosage chart |
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Indication | Form | Starting dosage | Standard dosage | Maximum dosage |
Type 2 diabetes mellitus | Metformin IR tablets | 850 mg once per day, OR 500 mg twice per day | 850-1000 mg twice per day | 2550 mg per day |
Metformin ER tablets | 500 mg taken at night | 1000-2000 mg per day | 2000 mg per day | |
Liquid suspension | 500 mg taken at night | 1000-2000 mg per day | 2550 mg per day | |
Type 2 diabetes mellitus prevention | Metformin IR tablets | 850 mg once per day for one month | 850 mg twice per day | 850 mg twice per day |
Metformin IR liquid solution | 850 mg once per day for one month | 850 mg twice per day | 850 mg twice per day | |
Polycystic ovary syndrome | Metformin IR tablets | 500 mg three times per day, OR 850-1000 mg twice per day | 500 mg three times per day, OR 850-1000 mg twice per day | 2550 mg per day |
Metformin ER tablets | 1500-2000 mg taken at night | 1500-2000 mg taken at night | 2000 mg per day | |
Metformin IR liquid solution | 500 mg three times per day | 850-1000 mg twice per day | 2550 mg per day |
The American Diabetes Association recommends metformin as a first-line agent in the management of Type 2 diabetes. Once initiated, metformin should be continued for as long as it is tolerated and not contraindicated. Other medications, such as SGLT2 inhibitors or glucagon-like peptide 1 (GLP-1) receptor agonists, should be added to metformin as needed for certain individuals with established cardiovascular risk, heart failure, or impaired kidney function.
Metformin is effective at lowering blood glucose, lowering hemoglobin A1C (a long-term marker of elevated blood glucose), improving cardiovascular mortality, and reducing cancer burden in individuals with Type 2 diabetes. Metformin exerts its glucose-lowering effects by decreasing hepatic glucose production, increasing insulin-mediated suppression of glucose production, and improving glucose uptake by peripheral tissues.
The metformin dose for Type 2 diabetes mellitus ranges between 500-2550 mg per day, depending on tolerance and glucose management. The initial doses of metformin should be taken with the evening meal.
There is some discussion around the use of metformin in individuals with prediabetes. By halting or reversing the progressive decline in insulin sensitivity and pancreatic beta cell function, metformin may prevent the onset of Type 2 diabetes in certain individuals. But some experts feel that metformin should not be used to treat prediabetes as most people with prediabetes do not develop diabetes, and many serious complications associated with diabetes may be absent in the prediabetic state.
The starting dose of metformin used in individuals with prediabetes is 850 mg of an immediate-release tablet taken for one month. This dosage may be increased to 850 twice a day.
RELATED: How to reverse prediabetes
PCOS is a hormonal condition where women experience menstrual irregularity, infertility, obesity, excess hair growth, and acne as a result of enlarged, cystic ovaries that overproduce androgens. While the exact cause of PCOS is unknown, there are some genetic components. Most women with PCOS have insulin resistance, which is related to the overproduction of testosterone in this condition.
Metformin treatment in PCOS is aimed at improving insulin sensitivity. Medications such as clomiphene citrate (to induce ovulation) or oral contraceptives (to prevent pregnancy and normalize menstrual cycles) may be used with metformin. While there is fair evidence that metformin alone is less effective than clomiphene citrate at ovulation induction, clinical data shows that metformin use in women with PCOS is associated with a higher rate of ovulation and pregnancy than placebo. The combination of metformin with clomiphene citrate is superior to metformin alone for ovulation induction.
For ovulation induction, metformin is typically taken as a 1500-2000 mg daily dose.
RELATED: Other PCOS treatments
Metformin may be used in children with Type 2 diabetes who are 10 years of age or older. Metformin is also used off-label in older children and adolescents with prediabetes or PCOS. Renal impairment in children requires dose adjustments. Avoid use in children with hepatic impairment.
Standard metformin dosage for children ages 10-16: 500-1000 mg twice per day
Standard metformin dosage for children ages 17 and older: 850-1000 mg twice per day
Metformin dosage by age |
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---|---|---|---|
Age | Starting dosage (IR tablet) | Standard dosage (IR liquid) | Maximum dosage (ER liquid) |
10-16 years of age | 500-1000 mg twice per day | 500-1000 mg twice per day | 500-2000 mg ER suspension per day |
17 years of age and older | 850-1000 mg twice per day | 850-1000 mg twice per day | 500-2000 mg ER suspension per day |
There are certain individuals who should not use metformin. There may also be certain times where individuals should discontinue the use of metformin for a short period of time.
Kidney function and estimated glomerular filtration rate (eGFR) should be assessed prior to beginning metformin. Individuals with an eGFR <30 ml/min should not use metformin. Metformin should not be started in patients with an eGFR between 30 to 45 ml/min.
Metformin has been issued a boxed warning for lactic acidosis by the FDA. Lactic acidosis is a very serious condition that occurs when there is an excess of lactate and its toxic metabolites in the blood. Metformin-associated lactic acidosis has resulted in death, hypothermia, low blood pressure, and abnormal heart rhythms.
Symptoms of metformin-associated lactic acidosis include malaise, muscle pain, respiratory distress, sleepiness, and abdominal pain.
Risk factors for metformin-associated lactic acidosis include poor renal function, drug interactions, age 65 years or older, imaging procedures with iodinated contrast, surgery, low oxygen states, excessive alcohol intake, and liver impairment. If lactic acidosis is suspected, stop metformin and seek medical attention.
While lactic acidosis is a very serious concern, the risk is extremely low (6 cases per 100,000 patient years) when metformin is taken at usual doses.
Metformin is contraindicated for use in:
Severe renal impairment (eGFR < 30)
Known hypersensitivity to the medication or other medications in the same class
A history of acute or chronic metabolic acidosis, including diabetic ketoacidosis
Low oxygen states
Dehydration
Sepsis
Surgery
Liver disease
Caution should be used in individuals who:
Have moderate renal impairment (eGFR 30-45)
Are 65 and older
Do not wish to be pregnant
Have heart failure
Use significant amounts of alcohol
Are at risk of low blood sugar
Metformin is not commonly used in veterinary medicine. Diabetes in dogs is typically attributed to lack of insulin production by pancreatic beta cells, which is closer to a Type 1 diabetes etiology than Type 2. Most case reports involving pets and metformin are regarding animals ingesting their owner’s medications and experiencing side effects of lactic acidosis as a result.
While metformin is generally a safe and effective medication, it is important to take this medication as prescribed in order to prevent unwanted side effects including hypoglycemia (low blood sugar) or lactic acidosis.
Follow medical advice while taking this medication. Inform your healthcare provider about any medications or supplements you are taking in order to minimize the risk of adverse effects from drug interactions.
Read the package insert and prescribing information.
The dose of this medication may be adjusted several times to see what works best.
This medication should be taken with food. When beginning this medication, it should be taken every day with the evening meal. Additional doses should be taken with the morning or afternoon meal.
If taking a liquid solution or suspension of this medication, measure the liquid with a marked spoon, oral syringe, or measuring cup. Shake the bottle well before measuring.
If taking this medication in tablet form, it is important to not crush, cut, or chew the tablets. Swallow the tablet whole.
Store this medication at room temperature (68-77 degrees Fahrenheit).
Do not consume alcohol in excessive amounts while taking this medication. Alcohol use is associated with an increased risk of lactic acidosis.
Consider taking vitamin B12 and folate supplements. Long-term metformin use is associated with decreased intestinal absorption of certain essential vitamins.
Speak with your healthcare provider about the correct way to discontinue this medication if you will be having surgery, another type of procedure that requires food or liquid restriction, or an imaging study with iodinated contrast.
Metformin is available as both an immediate-release and extended-release preparation. Extended-release metformin is sometimes used in individuals who are taking several medications to achieve glycemic control or who don’t tolerate the gastrointestinal side effects of metformin.
Immediate-release and extended-release metformin are typically dosed in the same range, around 1000 to 2000 mg per day.
The maximum dose of metformin is 2550 mg per day for adults and 2000 mg per day for children.
Many individuals take metformin for glucose control for years. There is some evidence that long-term, high-dose metformin use is associated with vitamin B12 deficiency. Vitamin supplements can help to prevent this.
RELATED: How to absorb vitamins better
Metformin should not be taken with alcohol. Alcohol may increase the risk of lactic acidosis. Additionally, alcohol and metformin together increase the risk of hypoglycemia and other negative side effects.
Published studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy. Metformin is sometimes used in pregnancy for the management of gestational diabetes. As strong evidence links high blood glucose with poor maternal and fetal outcomes, risk and benefits to both the mother and the developing fetus should be carefully weighed prior to beginning treatment.
RELATED: Gestational diabetes diet and treatment
Metformin is present in human breast milk. However, there is insufficient data to determine the effects of metformin on a breastfeeding infant. The developmental needs of the infant as well as the mother’s clinical need for metformin should be evaluated together when considering metformin use in nursing mothers.
Should metformin remain the first-line therapy for treatment of Type 2 diabetes?
Metformin-induced lactic acidosis with emphasis on the anion gap
Therapeutic use of metformin in prediabetes and diabetes prevention
Hypoglycemia and severe lactic acidosis in a dog following metformin exposure
Association between metformin dose and vitamin B12 deficient in patients with Type 2 diabetes
Metformin in pregnancy: mechanisms and clinical applications
Anne Jacobson, MD, MPH, is a board-certified family physician, writer, editor, teacher, and consultant. She is a graduate of University of Wisconsin School of Medicine and Public Health, and trained at West Suburban Family Medicine in Oak Park, Illinois. She later completed a fellowship in community medicine at PCC Community Wellness and a master's in Public Health at the University of Illinois-Chicago. She lives with her family near Chicago.
...Georgia C. Yalanis, MD, MSc, is a physician-scientist with expertise in “bench-to-bedside” medicine. She uses translational medicine applications to help clients and companies create products that are scientifically and technologically advanced while still being clinically useful. She has worked in the regulatory and biotech space and has a passion for individuals being empowered to make informed decisions about their medical and health care.
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