Metformin

• Metformin is used for treating type 2 diabetes in adults and children. It may be used alone or in combination with other diabetic medications.
• Metformin also has been used to prevent the development of diabetes in people at risk for diabetes, treatment of polycystic ovaries, and weight gain due to medications used for treating psychoses.

A small number of people who have taken metformin have developed a serious condition called lactic acidosis. Lactic acidosis is caused by a buildup of lactic acid in the blood. This happens more often in people with kidney problems. Most people with kidney problems should not take metformin. See "Side Effects".

Some conditions increase your chance of getting lactic acidosis, or cause other problems if you take metformin. Most of the conditions listed below can increase your chance of getting lactic acidosis.

Do not take metformin if you:

• have kidney problems
• have liver problems
• have heart failure that is treated with medicines, such as Lanoxin (digoxin) or Lasix (furosemide)
• drink a lot of alcohol. This means you binge drink for short periods or drink all the time.
• are seriously dehydrated (have lost a lot of water from your body)
• are going to have an x-ray procedure with injection of dyes (contrast agents)
• are going to have surgery
• develop a serious condition, such as heart attack, severe infection, or a stroke
• are 80 years or older and you have NOT had your kidney function tested

Do not drink a lot of alcohol drinks while taking this medication. This means you should not binge drink for short periods, and you should not drink a lot of alcohol on a regular basis. Alcohol can increase the chance of getting lactic acidosis.

Before receiving metformin, tell your doctor if you:

• have kidney problems
• have liver problems
• have heart failure that is treated with medicines, such as Lanoxin (digoxin) or Lasix (furosemide)
• drink a lot of alcohol. This means you binge drink for short periods or drink all the time.
• are seriously dehydrated (have lost a lot of water from your body)
• are going to have an x-ray procedure with injection of dyes (contrast agents)
• are going to have surgery
• develop a serious condition, such as heart attack, severe infection, or a stroke
• are 80 years or older and you have NOT had your kidney function tested
• are pregnant or breastfeeding

While taking metformin, tell your doctor if you

• have an illness that causes severe vomiting, diarrhea or fever, or if you drink a much lower amount of liquid than normal. These conditions can lead to severe dehydration (loss of water in your body). You may need to stop taking metformin for a short time.
• plan to have surgery or an x-ray procedure with injection of dye (contrast agent). You may need to stop taking metformin hydrochloride tablets for a short time.
• start to take other medicines or change how you take a medicine. Metformin can affect how well other drugs work, and some drugs can affect how well metformin works. Some medicines may cause high blood sugar.

In the U.S.

• Fortamet
• Glucophage
• Glucophage XR
• Glumetza
• Riomet

Available Dosage Forms:

• Tablet
• Tablet, Extended Release
• Solution

Therapeutic Class: Hypoglycemic

Chemical Class: Metformin

Metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 2 diabetes mellitus.

Total plasma Cl is decreased, half-life is prolonged, and Cmax is increased.

Refer to adult dosing. The initial and maintenance dosing should be conservative, due to the potential for decreased renal function (monitor).

Diabetes mellitus, type 2: Oral: Note: Allow 1 to 2 weeks between dose titrations: Clinically significant responses may not be seen at doses <1,500 mg daily; however, a lower recommended starting dose and gradual increased dosage is recommended to minimize gastrointestinal symptoms.

Immediate-release tablet or solution:

Children ≥10 years and Adolescents ≤16 years: Initial: 500 mg twice daily; increases in daily dosage should be made in increments of 500 mg at weekly intervals, given in divided doses, up to a maximum of 2,000 mg daily

Adolescents ≥17 years: Refer to adult dosing.

Extended-release tablet: Adolescents ≥17 years: Fortamet, Glucophage XR: Refer to adult dosing.

Oral: Administer with a meal (to decrease GI upset).

Extended release: Swallow whole; do not crush, break, or chew. Administer once daily doses with the evening meal. Fortamet should also be administered with a full glass of water.

Drug may cause GI upset; take with food (to decrease GI upset). Take at the same time(s) each day. Dietary modification based on ADA recommendations is a part of therapy. Monitor for signs and symptoms of vitamin B12 and/or folic acid deficiency; supplementation may be required.

You should not use metformin if you are allergic to it, or if you have:

• severe kidney disease; or

• if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin).

If you need to have any type of x-ray or CT scan using a dye that is injected into your veins, you will need to temporarily stop taking metformin.

To make sure metformin is safe for you, tell your doctor if you have:

• kidney disease;

• liver disease;

• a history of heart disease or recent heart attack;

• if you have recently taken chlorpropamide; or

• if you are over 80 years old and have not recently had your kidney function checked.

Some people taking metformin develop a serious condition called lactic acidosis. This may be more likely if you have liver or kidney disease, congestive heart failure, a severe infection, if you are dehydrated, or if you drink large amounts of alcohol. Talk with your doctor about your risk.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether metformin passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Metformin should not be given to a child younger than 10 years old. Extended-release formulations (Glucophage XR, Glumetza, Fortamet) are not approved for use by anyone younger than 18 years old.

Applies to metformin: compounding powder, oral solution, oral tablet, oral tablet extended release

General

Gastrointestinal events such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite have been frequently reported during therapy initiation and resolve spontaneously in most cases.

Adverse events in the pediatric population appear to be similar in nature and severity to that published in adults.[Ref]

Metabolic

Common (1% to 10%): Hypoglycemia
Very rare (less than 0.01%): Lactic acidosis[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (53.2%), nausea/vomiting (25.5%), flatulence (12.1%)
Common (1% to 10%): Indigestion, abdominal discomfort, abnormal stools, dyspepsia, loss of appetite[Ref]

Hematologic

Very rare (less than 0.01%): Subnormal vitamin B12 levels[Ref]

Other

Common (1% to 10%): Asthenia, chills, flu syndrome, accidental injury[Ref]

Hepatic

Very rare (less than 0.01%): Liver function test abnormalities, hepatitis[Ref]

Cardiovascular

Common (1% to 10%): Chest discomfort, flushing, palpitation[Ref]

Dermatologic

Common (1% to 10%): Rash, nail disorder, increased sweating
Very rare (less than 0.01%): Erythema, pruritus, urticaria[Ref]

Endocrine

Frequency not reported: Reduction in thyrotropin (TSH) levels[Ref]

Immunologic

Very common (10% or more): Infection (20.5%)[Ref]

Musculoskeletal

Common (1% to 10%): Myalgia[Ref]

Nervous system

Common (1% to 10%): Lightheadedness, taste disturbances[Ref]

Psychiatric

Common (1% to 10%): Headache[Ref]

Respiratory

Common (1% to 10%): Rhinitis[Ref]

Some side effects of metformin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Obtain eGFR prior to initiating therapy:
-eGFR less than 30 mL/min/1.73 m2: Use is contraindicated
-eGFR 30 to 45 mL/min/1.73 m2: Initiating therapy is not recommended
-eGFR that falls below 30 mL/min/1.73 m2 during therapy: Discontinue therapy
-eGFR that falls below 45 mL/min/1.73 m2 during therapy: Assess risks versus benefit of continued therapy
-eGFR greater than 45 mL/min/1.73 m2: No dose adjustments recommended

IODINATED CONTRAST PROCEDURE:
-For patients with eGFR between 30 and 60 mL/min/1.73 m2: Stop this drug at the time of, or before imaging procedure; re-evaluate eGFR 48 hours after procedure; restart therapy only if renal function is stable.

• Metformin is the preferred therapy for people with Type 2 diabetes. May be used in combination with other medications for Type 2 diabetes.
• May be used off-label (not an FDA-approved use, but still a recognized use of the drug) in polycystic ovary syndrome. Metformin decreases androgen hormone levels, improves menstrual cycles, ovulation regularity, and insulin sensitivity.
• Metformin rarely produces hypoglycemia (low blood sugar levels).
• Metformin does not change how much insulin is secreted and it does not cause hyperinsulinemia (high insulin levels). Fasting insulin levels and the base-line insulin response may actually decrease.
• Metformin has a unique mechanism of action and is like no other drug used for diabetes.
• Less likely to increase body weight (in fact body weight may decrease while on metformin), in contrast to many other medications used for diabetes, including sulfonylureas.
• May be used in children older than ten years.
• Generic metformin is available.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Diarrhea, nausea, flatulence, indigestion, headache, lack of energy, and taste disturbance are the most commonly reported side effects.
• Rarely, can cause lactic acidosis, a condition that can be fatal. The risk is higher in older people, those with kidney disease, taking other medications that may decrease kidney function, undergoing radiologic studies using contrast media, with liver disease or in those with other medical conditions such as congestive heart failure.
• May impair vitamin B12 absorption but rarely results in anemia.
• Excessive alcohol intake should be avoided because it can potentiate the risk of lactic acidosis.
• Should not be used in people with severe renal impairment. Metformin should not be initiated in people with an estimated glomerular filtration rate (eGFR) of less than 45 mL/min. The eGFR should be measured at least annually in people taking metformin.
• Should not be used in people with liver disease.
• Metformin may need to be temporarily discontinued in people with restricted food or fluid intake because continued use may increase the likelihood of dehydration, low blood pressure and kidney damage.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, click here.