Metformin

Metformin is a prescription medication used to treat the symptoms of Type 2 Diabetes Mellitus, together with diet and exercise to improve glycemic control in adults and pediatric patients 10 years or older. 

Metformin is available under the following different brand names: Glucophage, Glucophage XR, Glumetza, Riomet, Riomet ER.

Dosages of Metformin:

Adult dosage

Tablet, immediate-release

• 500mg (generic)
• 850mg (generic)
• 1000mg (generic)

Tablet, extended-release

• 500mg (generic, Glumetza)
• 750mg (generic)
• 1000mg (generic, Glumetza)

Oral solution

• 100mg/mL (Riomet)

Oral suspension, extended-release

• 47.31g/473mL per bottle (Riomet ER)
• reconstituted suspension is 500mg/5mL

Oral suspension

• 25mg/5mL

Pediatric dosage

Tablet, immediate-release

• 500mg (generic)
• 850mg (generic)
• 1000mg (generic)

Oral solution

• 100mg/mL (Riomet)

Oral suspension, extended-release

• 47.31g/473mL per bottle (Riomet ER)
• reconstituted suspension is 500mg/5mL 

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”.

Common side effects of Metformin include:

• low blood sugar, 
• nausea, 
• upset stomach, and
• diarrhea

Serious side effects of Metformin include:

• hives, 
• difficulty breathing, 
• swelling in your face, lips, tongue, or throat, 
• unusual muscle pain, 
• feeling cold, 
• trouble breathing, 
• dizziness, 
• lightheadedness, 
• tiredness, 
• weakness, 
• stomach pain, 
• vomiting, and
• slow or irregular heart rate

Rare side effects of Metformin include:

• none 

This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them.  Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

• Metformin has no known severe interactions with other drugs
• Metformin has serious interactions with at least 12 other drugs
• Metformin has moderate interactions with at least 194 other drugs  
• Metformin has mild interactions with at least 82 other drugs

This information does not contain all possible interactions or adverse effects.  Visit the RxList Drug Interaction Checker for any drugs interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use.  Keep a list of all your medications with you, and share this information with your doctor and pharmacist.  Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

• Lactic acidosis is a rare, but potentially severe, a consequence of therapy with metformin; it is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio; when metformin is implicated as the cause of lactic acidosis, metformin plasma concentrations >5 mcg/mL are generally found
• Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment; if metformin-associated lactic acidosis is suspected, immediately discontinue
• Patients with CHF requiring pharmacologic management, in particular those with unstable or acute CHF who are at risk for hypoperfusion and hypoxemia, are at an increased risk for lactic acidosis; the risk for lactic acidosis increases with the degree of renal dysfunction and the patient’s age
• Do not start in patients aged 80 years or older unless CrCl demonstrates that renal function is not reduced, because these patients are more susceptible to developing lactic acidosis; metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis
• Should generally be avoided in patients with clinical or laboratory evidence of hepatic disease; patients should be cautioned against excessive alcohol intake, either acute or chronic, during metformin therapy because alcohol potentiates the effects of metformin on lactate metabolism
• Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast
• The onset of lactic acidosis often is subtle and accompanied by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, increasing somnolence, nonspecific abdominal distress); with marked acidosis, hypothermia, hypotension, and resistant bradyarrhythmias may occur; patients should be instructed regarding recognition of these symptoms and told to notify their physician immediately if the symptoms occur; metformin should be withdrawn until the situation is clarified; serum electrolytes, ketones, blood glucose, and, if indicated, blood pH, lactate levels, and even blood metformin levels may be useful
• Once a patient is stabilized on any dose level of metformin, GI symptoms, which are common during initiation of therapy, are unlikely to be drug-related; later occurrences of GI symptoms could be due to lactic acidosis or another serious disease
• Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis who is lacking evidence of ketoacidosis (ketonuria and ketonemia); lactic acidosis is a medical emergency that must be treated in a hospital setting; in a patient with lactic acidosis who is taking metformin, the drug should be discontinued immediately and general supportive care measures promptly instituted; metformin is highly dialyzable (clearance up to 170 mL/min under good hemodynamic conditions); prompt hemodialysis is recommended to correct the acidosis and to remove the accumulated metformin; such management often results in prompt reversal of symptoms and recovery

Contraindications

• Hypersensitivity to metformin
• Chronic Heart Failure
• Diabetic ketoacidosis with or without coma
• Severe renal disease: eGFR less than 30 mL/min/1.73 m²
• Abnormal creatinine clearance resulting from shock, septicemia, or myocardial infarction
• Lactation

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Metformin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Metformin?”

Cautions

• Increased risk of severe hypoglycemia especially in elderly, debilitated or malnourished, adrenal or pituitary insufficiency, dehydration, heavy alcohol use, hypoxic states, hepatic/renal impairment, stress due to infection, fever, trauma, or surgery
• Concomitant administration of insulin and insulin secretagogues (e.g., sulfonylurea) may increase the risk of hypoglycemia; therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with metformin
• Withholding of food and fluids during surgical or other procedures may increase the risk for volume depletion, hypotension, and renal impairment; therapy should be temporarily discontinued while patients have restricted food and fluid intake
• Rare lactic acidosis may occur due to metformin accumulation; fatal in approximately 50% of cases; risk increases with age, degree of renal dysfunction, and with unstable or acute CHF; if metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of therapy; in patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin hydrochloride is dialyzable, with a clearance of up to170 mL/minute under good hemodynamic conditions); hemodialysis has often resulted in reversal of symptoms and recovery
• Possible increased risk of CV mortality
• May cause ovulation in anovulatory and premenopausal PCOS patients
• It May be necessary to discontinue therapy with metformin and administer insulin if the patient is exposed to stress (fever, trauma, infection), or experiences diabetic ketoacidosis
• Several of the postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia); cardiovascular collapse (shock) acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia; discontinue therapy when such events occur
• May impair vitamin B12 or calcium intake/absorption; monitor B12 serum concentrations periodically with long-term therapy
• Not indicated for use in patients with type 1 diabetes mellitus that are insulin-dependent due to lack of efficacy
• Withhold in patients with dehydration and/or prerenal azotemia
• Conclusive evidence of macrovascular risk reduction with metformin not established

Clinical recommendations based upon the patient’s renal function

• Before initiating therapy, obtain an eGFR
• Initiation of therapy is not recommended in patients with eGFR between 30-45 mL/minute/1.73 m²
• Obtain an eGFR at least annually in all patients receiving therapy
• In patients at increased risk for development of renal impairment (e.g., the elderly), renal function should be assessed more frequently
• If eGFR later falls below 45 mL/minute/1.73 m², assess the benefit and risk of continuing therapy

Iodinated contrast imaging procedures

• Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast
• Reevaluate eGFR after 48 hr after the imaging procedure; restart metformin if renal function is stable

Pregnancy and Lactation

• Limited data in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage; published studies with Metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk; poorly-controlled diabetes mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications; poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. 
• Limited published studies report that metformin is present in human milk; however, there is insufficient information to determine the effects of metformin on the breastfed infant and no available information on effects of metformin on milk production; therefore, developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and potential adverse effects on the breastfed child from therapy or the underlying maternal condition.