MetFORMIN (Lexi-Drugs)

ALERT: US Boxed Warning
  Lactic acidosis
Pronunciation

(met FOR min)

Brand Names: US

D-Care DM2 [DSC]; Fortamet; Glucophage; Glucophage XR; Glumetza; Riomet

Brand Names: Canada

ACT MetFORMIN; APO-MetFORMIN; APO-MetFORMIN ER; Auro-Metformin; DOM-MetFORMIN; ECL-MetFORMIN [DSC]; Glucophage; Glumetza; Glycon; JAMP-MetFORMIN; JAMP-MetFORMIN Blackberry; Mar-MetFORMIN [DSC]; MetFORMIN FC; MINT-MetFORMIN; MYLAN-MetFORMIN [DSC]; PHL-MetFORMIN [DSC]; PMS-MetFORMIN; PRO-MetFORMIN; Q-MetFORMIN [DSC]; RAN-MetFORMIN; RATIO-MetFORMIN; RIVA-MetFORMIN; SANDOZ MetFORMIN FC; Septa-MetFORMIN; TEVA-MetFORMIN [DSC]

Pharmacologic Category

Antidiabetic Agent, Biguanide

Dosing: Adult

Antipsychotic-induced weight gain, treatment (off-label use):

Immediate release: Oral: Dosage range studied in trials: 750 mg to 2 g daily in 2 to 3 divided doses. Doses up to 2.55 g/day have also been used. To minimize GI adverse effects, most trials initiated therapy with 250 mg or 500 mg twice daily or 850 mg once daily, and increased the dose gradually based on tolerability (Baptista 2007; Chen 2013; Das 2012; de Silva 2016; Jarskog 2013; Wang 2012; Zheng 2015).

Extended release: Oral: Maintenance dosage range in trials: 1 to 2 g once daily. To minimize GI adverse effects, trials initiated therapy with 500 mg once daily and titrated dosage upwards in 500 mg increments every 2 to 6 weeks based on tolerability (Carrizo 2009; Rado 2016).

Diabetes mellitus, type 2, prevention (off-label use): Note: For select patients with prediabetes, particularly for those with BMI ≥35 kg/m2, age <60 years, and women with prior gestational diabetes mellitus, in whom lifestyle interventions fail to improve glycemic indices (ADA 2018i; McCulloch 2018a).

Immediate release: Oral: Initial: 850 mg once daily for 1 month, then increase to 850 mg twice daily; unless GI adverse effects warrant a longer titration period (Knowler 2002)

Diabetes mellitus, type 2, treatment: Note: For patients who are not meeting glycemic targets despite diet, exercise, and metformin, combination therapy is necessary to achieve optimal results (McCulloch 2018b).

Immediate release: Oral:

Initial: 500 mg once or twice daily or 850 mg once daily (Nathan 2009)

Dosage adjustments: The dose should be increased gradually to minimize GI adverse effects. Titration strategies vary widely, but usually done in 500 mg or 850 mg increments every 7 days (range: 5 days to 1 month).

Usual maintenance dosage: 1 g twice daily or 850 mg twice daily (Nathan 2009)

Maximum: 2.55 g/day. Modest additional benefit has been observed with doses up to ~2.5 g/day; however, GI adverse effects may limit use (Nathan 2009). If doses >2 g/day are needed, consider administering in 3 divided doses to minimize GI adverse effects.

Extended release: Oral:

Initial: 500 mg to 1 g once daily

Dosage adjustments: The dose should be increased gradually to minimize GI adverse effects. Titration strategies vary widely, but usually done in 500 mg increments every 7 days (range: 7 days to 6 weeks).

Maximum: 2 g/day. If glycemic control is not achieved at maximum dose given once daily, may divide maximum dose and administer twice daily.

Gestational diabetes mellitus, treatment (alternative agent) (off-label use): Immediate release: Oral: Initial: 500 mg once or twice daily; increase dosage to meet glycemic targets, typically over 1 to 2 weeks, up to a maximum of 2 to 2.5 g daily in 2 to 3 divided doses. If targets not achieved with metformin alone, insulin may be added (Nachum 2017; Niromanesh 2012; Rowan 2008; Tertti 2013). Note: Insulin is the preferred medication for gestational diabetes as it does not cross the placenta to a measurable extent; all oral agents lack long-term safety data (ADA 2018c).

Polycystic ovary syndrome (PCOS): Note: Metformin is no longer recommended for anovulatory infertility in women with PCOS (ASRM 2017).

Oligomenorrhea due to PCOS, treatment (alternative agent) (off-label use): Immediate release: Oral: Dosage range studied in trials: 1.5 to 2 g daily in 2 to 3 divided doses; to minimize GI adverse effects, most trials initiated therapy with 500 mg once or twice daily and gradually increased the dose in 500 mg increments every 7 days (Costello 2007; Moghetti 2000; Morin-Papunen 2003; Nestler 2002). Note: Cyclic progestin therapy may be added for the first 6 months of metformin treatment, until regular cycles are established (Barbieri 2018).

Ovarian hyperstimulation syndrome (OHSS) in women with PCOS due to in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), prevention (alternative agent) (off-label use): Immediate release: Oral: Dosage range studied in trials: 1 to 2.55 g daily in 2 to 3 divided doses (Doldi 2006; Palomba 2011; Palomba 2013; Tang 2006; Tso 2014). Note: In most trials, metformin was used as a pretreatment and coadministered with gonadotropins; one trial coadministered metformin with gonadotropins only. Metformin was given until oocyte retrieval, hCG administration, or embryo transfer in most trials; in some trials, it was given until pregnancy test or 12 weeks’ gestation (Palomba 2013).

Metformin conversion recommendations:

Conversion from immediate-release to extended-release tablets: Patients receiving metformin immediate release may be switched to metformin extended release once daily at the same total daily dose, up to 2 g once daily. However, in patients who are doing well with immediate-release metformin, some experts recommend they continue using it, as there is little additional benefit documented with extended-release tablets (McCulloch 2018c).

Dosing: Geriatric

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

Dosing: Renal Impairment: Adult

eGFR >45 mL/minute/1.73 m2: No dosage adjustment necessary; monitor renal function at least annually. More frequent monitoring (every 3 to 6 months) and a maximum dose of 2 g/day has been recommended for patients with eGFR >45 to <60 mL/minute/1.73 m2 (ADA [Lipska 2011]; Inzucchi 2014).

eGFR 30 to 45 mL/minute/1.73 m2:

Preexisting impairment: Use is not recommended for initiation of therapy by some experts (AACE [Garber 2017]; ADA [Lipska 2011]; Inzucchi 2014); however, others recommend that in the absence of active kidney disease and/or conditions that predispose to hypoperfusion and hypoxemia (eg, acute heart failure, dehydration), therapy may be initiated at half the usual initial dose (eg, 250 mg/day) with close monitoring and titration (maximum: 1 g/day) (McCulloch 2018c).

If eGFR falls between 30 and <45 mL/minute/1.73 m2 during therapy: Consider benefits/risks of continuing therapy. If continuing therapy, a dosage reduction of 50% (maximum: 1 g/day) and monitoring of renal function every 3 months is recommended (ADA [Lipska 2011]; Inzucchi 2014).

eGFR <30 mL/minute/1.73 m2: Use is contraindicated.

Dosing: Hepatic Impairment: Adult

The manufacturer recommends avoiding metformin since liver disease is considered a risk factor for the development of lactic acidosis during metformin therapy. However, continued use of metformin in diabetic patients with liver dysfunction, including cirrhosis, has been used successfully and may be associated with a survival benefit in carefully selected patients; use cautiously in patients at risk for lactic acidosis (eg, renal impairment, alcohol use) (Brackett 2010; Zhang 2014).

Dosing: Pediatric

Diabetes mellitus, type 2; treatment: Note: Allow 1 to 2 weeks between dose titrations. Generally, clinically significant responses are not seen at doses less than 1,500 to 2,000 mg/day (AAP [Copeland 2013]); however, a lower recommended starting dose with a gradual increase in dosage is recommended to minimize gastrointestinal symptoms.

Immediate-release tablet or solution: Children ≥10 years and Adolescents: Oral: Initial: 500 to 1,000 mg once daily or 500 mg twice daily; increase dose every 1 to 2 weeks as tolerated in 500 to 1,000 mg increments; maximum dose: 1,000 mg twice daily or 850 mg 3 times daily (AAP [Copeland 2013]; ADA [Arslanian 2018]; ISPAD [Zeitler 2018]; manufacturer labeling)

Extended-release tablets: Note: Fewer gastrointestinal effects may be seen with extended-release products; however, no pediatric studies have compared extended-release products to standard metformin (ADA [Arslanian 2018]).

Children ≥10 years and Adolescents: Limited data available: Oral: Initial: 500 to 1,000 mg once daily for 7 to 14 days; may increase dose in 500 to 1,000 mg increments every 1 to 2 weeks as tolerated; maximum daily dose: 2,000 mg/day (AAP [Copeland 2013]; ADA [Arslanian 2018]; ISPAD [Zeitler 2018]). Note: If glycemic control is not achieved at maximum dose, may divide dose and administer twice daily.

Obesity: Severe, adjunct therapy with lifestyle interventions: Limited data available; data has shown modest efficacy (BMI reduction ~3%); optimal treatment duration not established; most trials 6 to 12 months in duration with largest BMI change usually observed in the first 3 to 4 months of therapy; a daily multivitamin supplement may be considered with therapy (AHA [Kelly 2013]; Matson 2012; McDonagh 2014):

Immediate release: Dosing regimens variable: Children ≥6 years and Adolescents: Oral: Initial: 500 mg once or twice daily, titrate upward at weekly intervals by 500 mg/day increments to a target dose of 1,000 mg administered in the morning and 500 mg in the evening or 1,000 mg twice daily (Kendall 2013; Yanovski 2011); several other trials have reported doses of 500 mg twice daily dosing (Matson 2012)

Extended release: Metformin XR: Adolescents: Oral: Initial: 500 mg once daily with dinner for 2 weeks; increase to 1,000 mg once daily for 2 weeks, and then 2,000 mg once daily; may slow titration if adverse gastrointestinal effects; treatment continued for a total of 48 weeks (Glaser Pediatric Research Network [Wilson 2010])

Dosing: Renal Impairment: Pediatric

Children ≥10 years and Adolescents:

eGFR >45 mL/minute/1.73 m2: No dosage adjustment necessary

eGFR 30 to 45 mL/minute/1.73 m2:

Preexisting impairment: Initiation of therapy is not recommended

If eGFR falls between 30 and <45 mL/minute/1.73 m2 during therapy: Consider risk/benefit ratio for continuing therapy

eGFR <30 mL/minute/1.73 m2: Use is contraindicated

Dosing: Hepatic Impairment: Pediatric

Children ≥10 years and Adolescents: Avoid metformin; liver disease is a risk factor for the development of lactic acidosis during metformin therapy.

Use: Labeled Indications

Diabetes mellitus, type 2: Management of type 2 diabetes mellitus when hyperglycemia cannot be managed with diet and exercise alone.

Note: If not contraindicated and if tolerated, metformin is the preferred initial pharmacologic agent for type 2 diabetes management (ADA 2018a).

Use: Off-Label: Adult

  Antipsychotic-induced weight gainLevel of Evidence [B, G]

Data from multiple meta-analyses of randomized controlled trials with varying degrees of heterogeneity (primarily in patients with schizophrenia and schizoaffective disorder) support the use of metformin in promoting modest weight loss and preventing weight gain associated with second-generation antipsychotics in adult patients Ref. Additional trials may be necessary to further define the role of metformin in this condition.

Based on British Association for Psychopharmacology guidelines on the management of weight gain, metabolic disturbances, and cardiovascular risk associated with psychosis and antipsychotic drug treatment, metformin should be considered to attenuate or reduce weight gain caused by antipsychotics after behavioral interventions have failed Ref. Based on the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommendations for the management of patients with mood disorders and comorbid metabolic disorders, metformin is recommended as a second-line option after nonpharmacologic strategies for managing weight gain in patients with bipolar and major depressive disorders have failed, and is recognized as often being used as a secondary prevention strategy for antipsychotic-related weight gain RefAccess Full Off-Label Monograph

  Diabetes mellitus, type 2 (prevention)Level of Evidence [A, G]

Data from a multicenter, placebo-controlled clinical trial involving 3,234 nondiabetic patients at high risk for developing diabetes showed that metformin treatment reduced the incidence of diabetes compared to placebo Ref.

Based on the American Diabetic Association (ADA) Standards of Medical Care in Diabetes, metformin is effective and may be considered for the prevention of type 2 diabetes in patients with prediabetes (ie, impaired glucose tolerance [IGT], impaired fasting glucose [IFG], or an HbA1c 5.7% to 6.4%), especially for those with BMI ≥35 kg/m2, those <60 years of age, and women with prior gestational diabetes mellitus.

Based on the Endocrine Society guidelines for the diagnosis and treatment of polycystic ovary syndrome (PCOS), metformin is recommended for prevention of type 2 diabetes in women with PCOS and IGT when lifestyle modification has not been successful Ref.

  Gestational diabetes mellitus (GDM) (treatment)Level of Evidence [G]

Based on the American Diabetic Association (ADA) Standards of Medical Care in Diabetes, metformin may be considered an option in the treatment of gestational diabetes mellitus based on short-term safety and efficacy studies. However, because long-term safety data are not available, insulin is the preferred treatment when pharmacologic therapy is needed.

  Polycystic ovary syndrome (PCOS): Oligomenorrhea due to PCOS (treatment)Level of Evidence [B, G]

Data from controlled trials and meta-analyses indicate that metformin may improve menstrual patterns in some women with PCOS, but metformin is less effective than combination oral contraceptives. It is unknown whether the improvement in ovulation rate from metformin is associated with a risk reduction for endometrial carcinoma. Additional trials may be necessary to further define the role of metformin in this condition.

Endocrine Society clinical guidelines on PCOS consider metformin a second-line therapy for menstrual irregularities in women who cannot take or tolerate hormonal contraception. Access Full Off-Label Monograph

  Polycystic ovary syndrome: Ovarian hyperstimulation syndrome (OHSS) in women with PCOS due to in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) (prevention)Level of Evidence [B, G]

Controlled trials and meta-analyses indicate that metformin significantly reduces the risk of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovary syndrome (PCOS) receiving a gonadotropin during IVF. The number needed to treat for metformin to prevent one case of OHSS is 5. Additional trials may be necessary to further define the role of metformin in this condition.

Endocrine Society guidelines for management of PCOS suggest using metformin as adjuvant therapy to prevent OHSS in women with PCOS undergoing IVF. Access Full Off-Label Monograph

Level of Evidence Definitions
  Level of Evidence Scale
Use: Unsupported: Adult
Polycystic ovary syndrome: Anovulatory infertility

Based on currently available evidence, metformin is no longer recommended for anovulatory infertility in women with polycystic ovary syndrome (PCOS). The American Society for Reproductive Medicine states although there is evidence that metformin alone increases the ovulation rate in women with PCOS, there is insufficient evidence to suggest that metformin alone increases pregnancy rates or live-birth rates when compared with placebo (ASRM 2017) . A randomized, controlled trial has shown metformin does not increase live-birth rates when compared to clomiphene citrate alone in women with PCOS (Legro 2007). A consensus group stated that metformin use in PCOS should be restricted to women with glucose intolerance (Thessaloniki 2008).

Clinical Practice Guidelines

Diabetes Mellitus:

American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE), “Consensus Statement on the Comprehensive Type 2 Diabetes Management Algorithm – 2018 Executive Summary,” January 2018

American Diabetes Association, “Standards of Medical Care in Diabetes – 2018,” January 2018

Diabetes Canada, “Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada,” 2018

Prevention:

“AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and Other Atherosclerotic Vascular Disease: 2011 Update,” November 2011

Metabolic disorders:

British Association of Psychopharmacology (BAP), “BAP Guidelines on the Management of Weight Gain, Metabolic Disturbances and Cardiovascular Risk Associated With Psychosis and Antipsychotic Drug Treatment,” August 2016

Canadian Network for Mood and Anxiety Treatments (CANMAT), “Recommendations for the Management of Patients with Mood Disorders and Comorbid Metabolic Disorders,” February 2012

Administration: Oral

Administer with a meal (to decrease GI upset). Administer Riomet with supplied dosing cup.

Extended release: Swallow whole; do not crush, cut, or chew. Administer once daily doses with the evening meal.

Administration: Pediatric

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

Immediate release: Glucophage, Riomet: Administer in divided doses with meals. Administer Riomet with supplied dosing cup.

Extended release: Fortamet, Glucophage XR, Glumetza: Administer once-daily doses with the evening meal; swallow whole; do not cut, crush, or chew; Fortamet should also be administered with a full glass of water

Dietary Considerations

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.

Storage/Stability

Oral solution: Store at 15°C to 30°C (59°F to 86°F).

Tablets: Store at 20°C to 25°C (68°F to 77°F); excursion permitted to 15°C to 30°C (59°F to 86°F). Protect from light and moisture.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea, flatulence, nausea, vomiting, headache, or loss of strength and energy. Have patient report immediately to prescriber signs of lactic acidosis (fast breathing, tachycardia, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), or severe abdominal pain (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer:Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  International issues:
Contraindications

US labeling: Hypersensitivity to metformin or any component of the formulation; severe renal dysfunction (eGFR <30 mL/minute/1.73 m2); acute or chronic metabolic acidosis with or without coma (including diabetic ketoacidosis)

Canadian labeling: Hypersensitivity to metformin or any component of the formulation; renal function unknown, renal impairment, and serum creatinine levels above the upper limit of normal range; renal disease or renal dysfunction (serum creatinine ≥136 micromol/L in males or ≥124 micromol/L in females or abnormal creatinine clearance <60 mL/minute) which may result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia; unstable and/or insulin-dependent (type I) diabetes mellitus; acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma, history of ketoacidosis with or without coma; history of lactic acidosis (regardless of precipitating factors); excessive alcohol intake (acute or chronic); severe hepatic dysfunction or clinical or laboratory evidence of hepatic disease; cardiovascular collapse and disease states associated with hypoxemia including cardiorespiratory insufficiency, which are often associated with hyperlactacidemia; stress conditions (eg, severe infection, trauma, surgery and postoperative recovery phase); severe dehydration; pregnancy; breastfeeding

Warnings/Precautions

Concerns related to adverse effects:

• Lactic acidosis: [US Boxed Warning]: Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset is often subtle, accompanied by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, somnolence, abdominal pain); elevated blood lactate levels (>5 mmol/L); anion gap acidosis (without evidence of ketonuria or ketonemia); increased lactate:pyruvate ratio; metformin plasma levels generally >5 mcg/mL. Risk factors for lactic acidosis include patients with renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), ≥65 years, having a radiologic study with contrast, surgery and other procedures, hypoxic states (eg, acute heart failure), excessive alcohol intake, and hepatic impairment. Discontinue immediately if lactic acidosis is suspected; prompt hemodialysis is recommended. Lactic acidosis should be suspected in any patient with diabetes receiving metformin with evidence of acidosis but without evidence of ketoacidosis. Discontinue use in patients with conditions associated with dehydration, hypoperfusion, sepsis, or hypoxemia. Temporarily discontinue therapy in patients with restricted food and fluid intake. The risk of accumulation and lactic acidosis increases with the degree of impairment of renal function.

• Vitamin B12 concentrations: Long-term metformin use is associated with vitamin B12 deficiency; monitor vitamin B12 serum concentrations periodically with long-term therapy. Monitoring of B12 serum concentrations should be considered in all patients receiving metformin and in particular those with peripheral neuropathy or anemia (ADA 2018d).

Disease-related concerns:

• Heart failure: Metformin may be used in patients with stable heart failure (HF); avoid use in unstable or hospitalized patients with heart failure (ADA 2018h). Risk of lactic acidosis may be increased secondary to hypoperfusion. In a scientific statement from the American Heart Association, metformin has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]). Use of metformin in patients with HF may be associated with reduced mortality and reduction in hospital readmission for HF (Crowley 2017; Eurich 2013).

• Hepatic impairment: The manufacturer recommends to generally avoid use in patients with hepatic impairment due to potential for lactic acidosis. However, continued use of metformin in patients with diabetes with liver dysfunction, including cirrhosis, may be associated with a survival benefit in carefully selected patients (Brackett 2010; Crowley 2017; Zhang 2014).

• Renal impairment: Metformin is substantially excreted by the kidney; assess renal function prior to initiation of therapy and periodically thereafter using estimated glomerular filtration rate (eGFR); the risk of metformin accumulation and lactic acidosis increases with degree of renal impairment. Use is contraindicated in patients with eGFR <30 mL/minute/1.73 m2. Assess benefits/risks of metformin use in patients with eGFR 30 to 45 mL/minute/1.73 m2; if used, dosage reduction is recommended (ADA [Lipska 2011]; Inzucchi 2014; McCulloch 2018c). Some experts recommend avoiding initiation of metformin in these patients (AACE [Garber 2017]; ADA [Lipska 2011]; Inzucchi 2014), while others suggest initiation may be reasonable in the absence of active kidney disease and/or conditions that predispose to hypoperfusion and hypoxemia (McCulloch 2018c). Use of concomitant medications that may affect renal function (ie, affect tubular secretion) may also affect metformin disposition. Metformin should be withheld in patients with dehydration and/or prerenal azotemia.

• Stress-related states: It may be necessary to discontinue metformin and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution; risk of metformin associated lactic acidosis increases with age.

Dosage form specific issues:

• Extended-release tablet: Insoluble tablet shell (Glumetza 1,000 mg tablet) may remain intact and be visible in the stool. Other extended-release tablets (Fortamet, Glucophage XR, Glumetza 500 mg) may appear in the stool as a soft mass resembling the tablet.

Other warnings/precautions:

• Appropriate useNot indicated for use in patients with type 1 diabetes mellitus or with diabetic ketoacidosis (DKA).

• Ethanol use: Instruct patients to avoid excessive acute or chronic ethanol use; ethanol may potentiate metformin’s effect on lactate metabolism.

• Iodinated contrast: According to the manufacturer, it is recommended to temporarily discontinue metformin at the time of or before iodinated contrast imaging procedures in patients with an eGFR 30 to 60 mL/minute/1.73 m2; or with a history of hepatic disease, alcoholism, or heart failure; or in patients who will receive intra-arterial iodinated contrast. Reevaluate eGFR 48 hours after imaging procedure; restart if renal function is stable. Alternatively, the American College of Radiology (ACR) guidelines recommend that metformin may be used prior to or following administration of iodinated contrast media in patients with no evidence of acute kidney injury (AKI) and with an eGFR ≥30 mL/minute/1.73 m2; ACR guidelines recommend temporary discontinuation of metformin in patients with known AKI or severe chronic kidney disease ([stage IV or V [ie, eGFR <30 mL/minute/1.73 m2]) or who are undergoing arterial catheter studies (ACR 2017).

• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.

• Surgical procedures: Metformin should be withheld the day of surgery (all other oral hypoglycemic agents should be withheld the morning of surgery or procedure) (ADA 2018e). Restart only after normal oral intake resumed and normal renal function is verified.

Geriatric Considerations

Limited data suggest that metformin’s total body clearance may be decreased and AUC and half-life increased in elderly patients; presumably due to decreased renal clearance. Metformin has been well tolerated by the elderly but lower doses and frequent monitoring are recommended. In one study of elderly subjects, its effects could not be distinguished from tolbutamide, except for weight loss. The initial and maintenance dosing should be conservative, due to the potential for decreased renal function. Generally, elderly patients should not be titrated to the maximum dose of metformin. eGFR ≥30 mL/minute/1.73 m2 (ADA 2018b), but it continues to be contraindicated in patients with advanced renal insufficiency (eGFR <30 mL/minute/1.73 m2) (See Dosing: Renal Impairment for specific recommendations for patients whose eGFR is ≥30 mL/minute/1.73 m2 and <60 mL/minute/1.73 m2). Older adults with diabetes are at a higher risk of cognitive decline and institutionalization (ADA 2018b).

Intensive glucose control (HbA1c <6.5%) has been linked to increased all-cause and cardiovascular mortality, hypoglycemia requiring assistance, and weight gain in adult type 2 diabetes. How “tightly” to control a geriatric patient’s blood glucose needs to be individualized. Such a decision should be based on several factors, including the patient’s functional and cognitive status, how well he/she recognizes hypoglycemic or hyperglycemic symptoms, and how to respond to them and other disease states. An HbA1c <7.5% is an acceptable endpoint for a healthy older adult, while <8% to 8.5% is acceptable for elderly patients depending on the level of comorbidities, functional and cognitive status and living situation (eg, caregiver present to assist, long-term care facility). For elderly patients with diabetes who are relatively healthy, attaining target goals for aspirin use, blood pressure, lipids, smoking cessation, and diet and exercise may be more important than normalized glycemic control (ADA 2018b).

Older adults are more likely to experience vitamin B12 deficiency with long-term use of metformin (Kancherla 2017). Monitoring of B12 levels at baseline and yearly thereafter (or sooner if symptoms of deficiency are present) is a prudent recommendation for those on metformin.

When extended-release metformin is being considered, swallowing ability should be assessed due to the inability to crush this formulation.

Pregnancy Considerations

Metformin crosses the placenta; concentrations may be comparable to those found in the maternal plasma (Charles 2006; de Oliveira Baraldi 2011; Eyal 2010; Vanky 2005).

An increased risk of birth defects or adverse fetal/neonatal outcomes has not been observed following maternal use of metformin for gestational diabetes mellitus or type 2 diabetes mellitus when glycemic control is maintained (Balani 2009; Coetzee 1979; Coetzee 1984; Ekpebegh 2007; Niromanesh 2012; Rowan 2008; Rowan 2010; Tertti 2008). However, available guidelines note that long-term safety data are not available (ACOG 190 2018; ACOG 201 2018; ADA 2018c). In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and mother (ACOG 201 2018; ADA 2018c; Metzger 2007).

To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2018c; Blumer 2013). Agents other than metformin are currently recommended to treat diabetes in pregnant women (ADA 2018c). However metformin may be used as an alternative agent in some patients requiring therapy for gestational diabetes mellitus or type 2 diabetes mellitus (ACOG 190 2018; ACOG 201 2018). Pharmacokinetic studies suggest that clearance of metformin may increase during pregnancy and dosing may need adjusted in some women when used during the third trimester (Charles 2006; Eyal 2010; Gardiner 2003; Hughes 2006; Vanky 2005).

Breast-Feeding Considerations

Metformin is present in breast milk.

The relative infant dose (RID) of metformin is 1.08% when calculated using the highest average breast milk concentration located and compared to a weight-adjusted maternal dose of 6.55 mg/kg/day.

In general, breastfeeding is considered acceptable when the RID is <10 (Anderson 2016; Ito 2000).

The RID of metformin was calculated using a milk concentration of 0.47 mcg/mL, providing an estimated daily infant dose via breast milk of 0.07 mg/kg/day. This milk concentration was obtained following maternal administration of metformin 500 mg twice daily and the RID was calculated using the actual weight of the woman in the study (Briggs 2005).

Small amounts of metformin have been detected in the serum of breastfeeding infants. Because breast milk concentrations of metformin stay relatively constant, avoiding breastfeeding around peak plasma concentrations in the mother would not be helpful in reducing metformin exposure to the infant (Briggs 2005; Eyal 2010; Gardiner 2003; Hale 2002).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, benefits of breastfeeding to the infant, and benefits of treatment to the mother. However, breastfeeding is encouraged for all women, including those with diabetes (ACOG 201 2018; ADA 2018c; Blumer 2013; Metzger 2007). Metformin may be used in breastfeeding women (Blumer 2013).

Lexicomp Pregnancy & Lactation, In-Depth
Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

>10%:

Gastrointestinal: Diarrhea (IR tablet: 12% to 53%; ER tablet: 10% to 17%), nausea and vomiting (IR tablet: 26%; ER tablet: 7%), flatulence (4% to 12%)

Infection: Infection (21%)

1% to 10%:

Cardiovascular: Chest discomfort, flushing, palpitations

Central nervous system: Headache (5% to 6%), chills, dizziness, taste disorder

Dermatologic: Diaphoresis, nail disease, skin rash

Endocrine & metabolic: Decreased vitamin B12 serum concentrate (7%), hypoglycemia

Gastrointestinal: Nausea (7% to 9%), dyspepsia (≤7%), abdominal distress (6%), abdominal pain (3% to 4%), abdominal distention, abnormal stools, constipation, heartburn

Neuromuscular & skeletal: Weakness (9%), myalgia

Respiratory: Rhinitis (4% to 6%), dyspnea, flu-like symptoms, upper respiratory tract infection

Miscellaneous: Accidental injury (6% to 7%)

<1%, postmarketing and/or case reports: Hepatic injury (cholestatic, hepatocellular, and mixed), lactic acidosis

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Substrate of OCT2

Drug Interactions 

Abemaciclib: May increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of MetFORMIN. Specifically, alcohol may potentiate the risk of lactic acidosis Risk X: Avoid combination

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Risk C: Monitor therapy

Bictegravir: May increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk of developing lactic acidosis may be increased. Exceptions: Brinzolamide; Dorzolamide. Risk C: Monitor therapy

Cephalexin: May increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of MetFORMIN. Management: Consider alternatives to cimetidine in patients receiving metformin due to a potential for increased metformin concentrations and toxicity (including lactic acidosis). Risk D: Consider therapy modification

Dalfampridine: MetFORMIN may increase the serum concentration of Dalfampridine. Dalfampridine may increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Dofetilide: MetFORMIN may increase the serum concentration of Dofetilide. Risk C: Monitor therapy

Dolutegravir: May increase the serum concentration of MetFORMIN. Management: Limit the daily metformin dose to 1,000 mg when used with dolutegravir. Monitor for increased metformin effects/toxicities during concomitant use. Risk D: Consider therapy modification

Glycopyrrolate (Systemic): May increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Iodinated Contrast Agents: May enhance the adverse/toxic effect of MetFORMIN. Renal dysfunction that may be caused by iodinated contrast agents may lead to metformin-associated lactic acidosis. Management: Management advice varies. Refer to the full drug interaction monograph content for details. Exceptions: Diatrizoate Meglumine; Diatrizoate Sodium; Ethiodized Oil. Risk D: Consider therapy modification

Isavuconazonium Sulfate: May increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

LamoTRIgine: May increase the serum concentration of MetFORMIN. Management: The lamotrigine Canadian product monograph states that coadministration of these drugs is not recommended. Risk C: Monitor therapy

Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C: Monitor therapy

Ombitasvir, Paritaprevir, and Ritonavir: May enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk for lactic acidosis may be increased. Risk C: Monitor therapy

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk for lactic acidosis may be increased. Risk C: Monitor therapy

Ondansetron: May increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

Patiromer: May decrease the serum concentration of MetFORMIN. Management: Administer metformin at least 3 hours before or 3 hours after patiromer. Risk D: Consider therapy modification

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C: Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C: Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy

Ranolazine: May increase the serum concentration of MetFORMIN. Management: Limit the metformin dose to a maximum of 1700 mg/day when used together with ranolazine 1000 mg twice daily. Risk D: Consider therapy modification

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C: Monitor therapy

Tafenoquine: May increase the serum concentration of MATE1 Substrates. Management: Avoid use of MATE substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the MATE substrate and consider a reduced dose of the MATE substrate according to that substrate’s labeling. Risk D: Consider therapy modification

Tafenoquine: May increase the serum concentration of OCT2 Substrates. Management: Avoid use of OCT2 substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the OCT2 substrate and consider a reduced dose of the OCT2 substrate according to that substrate’s labeling. Risk D: Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Topiramate: May enhance the adverse/toxic effect of MetFORMIN. Risk C: Monitor therapy

Trimethoprim: May increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

Trospium: MetFORMIN may decrease the serum concentration of Trospium. Risk C: Monitor therapy

Vandetanib: May increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

Verapamil: May diminish the therapeutic effect of MetFORMIN. Risk C: Monitor therapy

Food Interactions

Food decreases the extent and slightly delays the absorption. Management: Administer with a meal.

Monitoring Parameters

Urine for glucose and ketones, fasting blood glucose, hemoglobin A1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2018g]). Initial and annual monitoring of hematologic parameters (eg, hemoglobin/hematocrit and red blood cell indices); renal function (eGFR) prior to therapy initiation and at least annually (more often in patients at risk of developing renal impairment; every 3 to 6 months if eGFR 45 to <60 mL/minute/1.73 m2; every 3 months if eGFR 30 to <45 mL/minute/1.73 m2 [Lipska 2011]). Monitor vitamin B12 serum concentrations every 2 to 3 years; folate (if megaloblastic anemia is suspected).

Reference Range

Recommendations for glycemic control in nonpregnant adults with diabetes (ADA 2018g):

HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics)

Preprandial capillary blood glucose: 80 to 130 mg/dL

Peak postprandial capillary blood glucose: <180 mg/dL

Recommendations for glycemic control in older adults (≥65 years) with diabetes (ADA 2018b):

HbA1c: <7.5% (healthy); <8% (complex/intermediate health); <8.5% (very complex/poor health) (individualization may be appropriate based on patient and caregiver preferences)

Preprandial capillary blood glucose: 90 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health)

Bedtime capillary blood glucose: 90 to 150 mg/dL (healthy); 100 to180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health)

Recommendations for glycemic control in pediatric (all age groups) patients (ADA 2018f): HbA1c: <7.5% (individualization may be appropriate based on patient-specific characteristics; <7% is reasonable if it can be achieved without excessive hypoglycemia)

Advanced Practitioners Physical Assessment/Monitoring

Obtain HbA1c (twice yearly in stable patients and quarterly in unstable patients), serum glucose, hematologic parameters, liver function tests (baseline), and renal function tests (baseline and annually or more frequently in patients at risk for renal impairment). Check urine for glucose and ketones. Assess for signs and symptoms of vitamin B12 and/or folic acid deficiency during therapy; supplementation may be required. Assess for signs and symptoms of metabolic acidosis. Refer patient to diabetes educator for diabetes self-management education.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Watch for signs of hypoglycemia. Refer patient to diabetes educator for diabetes self-management education. Educate patient about increased risk of metabolic acidosis and to report any signs or symptoms (malaise, myalgias, respiratory distress, excessive drowsiness, and abdominal pain).

Dosage Forms Considerations

Extended release tablets utilize differing release mechanisms: Glucophage XR uses dual hydrophilic polymer matrix systems, Fortamet uses single-composition osmotic technology, and Glumetza uses gastric retention technology.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Kit, Combination:

D-Care DM2: Extended release tablet, as hydrochloride: 500 mg [DSC]

Solution, Oral, as hydrochloride:

Riomet: 500 mg/5 mL (118 mL, 473 mL) [contains propylene glycol; strawberry flavor]

Riomet: 500 mg/5 mL (118 mL, 473 mL) [contains saccharin calcium; cherry flavor]

Generic: 500 mg/5 mL (473 mL)

Tablet, Oral, as hydrochloride:

Glucophage: 500 mg, 850 mg

Glucophage: 1000 mg [scored]

Generic: 500 mg, 850 mg, 1000 mg

Tablet Extended Release 24 Hour, Oral, as hydrochloride:

Fortamet: 500 mg, 1000 mg

Glucophage XR: 500 mg, 750 mg

Glumetza: 500 mg, 1000 mg

Generic: 500 mg, 750 mg, 1000 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Glucophage: 500 mg, 850 mg

Glycon: 500 mg, 850 mg

Generic: 500 mg, 850 mg

Tablet Extended Release 24 Hour, Oral, as hydrochloride:

Glumetza: 500 mg

Glumetza: 1000 mg [contains FD&C BLUE #2 (INDIGOTINE), FD&C RED #40, FD&C YELLOW #6 (SUNSET YELLOW)]

Generic: 500 mg, 1000 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • A10BA02
Generic Available (US)

May be product dependent

Pricing: US

Solution (metFORMIN HCl Oral)

500 mg/5 mL (per mL): $1.69

Solution (Riomet Oral)

500 mg/5 mL (per mL): $1.69

Tablet, 24-hour (Fortamet Oral)

500 mg (per each): $42.17

1000 mg (per each): $42.17

Tablet, 24-hour (Glucophage XR Oral)

500 mg (per each): $1.21

750 mg (per each): $1.81

Tablet, 24-hour (Glumetza Oral)

500 mg (per each): $61.78

1000 mg (per each): $133.60

Tablet, 24-hour (metFORMIN HCl ER (MOD) Oral)

500 mg (per each): $55.59 – $55.60

1000 mg (per each): $120.22 – $120.24

Tablet, 24-hour (metFORMIN HCl ER (OSM) Oral)

500 mg (per each): $9.08 – $17.24

1000 mg (per each): $17.13 – $31.40

Tablet, 24-hour (metFORMIN HCl ER Oral)

500 mg (per each): $0.75 – $1.03

750 mg (per each): $1.20 – $1.54

Tablets (Glucophage Oral)

500 mg (per each): $1.18

850 mg (per each): $2.01

1000 mg (per each): $2.44

Tablets (metFORMIN HCl Oral)

500 mg (per each): $0.03 – $0.71

850 mg (per each): $0.07 – $1.20

1000 mg (per each): $0.08 – $1.45

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity (increases peripheral glucose uptake and utilization)

Pharmacodynamics/Kinetics

Onset of action: Within days; maximum effects up to 2 weeks

Distribution: Vd: 654 ± 358 L; partitions into erythrocytes; concentrates in liver, kidney, and GI tract

Protein binding: Negligible

Metabolism: Not metabolized by the liver

Bioavailability: Absolute: Fasting: 50% to 60%

Half-life elimination: Plasma: 4 to 9 hours; Blood ~17.6 hours

Time to peak, serum: Immediate release: 2 to 3 hours; Extended release: 7 hours (range: 4 to 8 hours)

Excretion: Urine (90% as unchanged drug; active secretion)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Peak and systemic exposure is increased and oral and renal clearance is decreased.

Geriatric: Total plasma clearance is decreased, half-life is prolonged, and Cmax is increased.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Taste disorder.

Metformin-dependent patients with diabetes (noninsulin dependent, Type 2) should be appointed for dental treatment in morning in order to minimize chance of stress-induced hypoglycemia.

Effects on Bleeding

No information available to require special precautions

Index Terms

Metformin HCl; Metformin Hydrochloride

FDA Approval Date
December 29, 1994
References

American Association of Clinical Endocrinologists Polycystic Ovary Syndrome Writing Committee, “American Association of Clinical Endocrinologists Position Statement on Metabolic and Cardiovascular Consequences of Polycystic Ovary Syndrome,” Endocr Pract, 2005, 11(2):126-34.[PubMed 15915567]

American College of Obstetricians and Gynecologists ACOG Practice Bulletin No. 201: Pregestational Diabetes Mellitus. Obstet Gynecol. 2018;132(6):e228-e248. doi: 10.1097/AOG.0000000000002960.[PubMed 30461693]

American College of Obstetricians and Gynecologists (ACOG) ACOG Practice Bulletin No. 194: Polycystic Ovary Syndrome. Obstet Gynecol. 2018;131(6):e157-e171. doi: 10.1097/AOG.0000000000002656.[PubMed 29794677]

American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018;131(2):e49-e64.[PubMed 29370047]

American College of Radiology Committee on Drugs and Contrast Media. ACR Manual on Contrast Media. Version 10.3. https://www.acr.org/Clinical-Resources/Contrast-Manual. Published 2017. Accessed January 3, 2018.

American Diabetes Association (ADA). 8. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2018. Diabetes Care. 2018a;41(suppl 1):S73-S85. doi: 10.2337/dc18-S008.[PubMed 29222379]

American Diabetes Association (ADA). 11. Older adults: standards of medical care in diabetes-2018. Diabetes Care. 2018b;41(suppl 1):S119-S125. doi: 10.2337/dc18-S011.[PubMed 29222382]

American Diabetes Association (ADA). 13. Management of diabetes in pregnancy: standards of medical care in diabetes-2018. Diabetes Care. 2018c;41(suppl 1):S137-S143. doi: 10.2337/dc18-S013.[PubMed 29222384]

American Diabetes Association (ADA). 4. Lifestyle management: standards of medical care in diabetes-2018. Diabetes Care. 2018d;41(suppl 1):S38-S50. doi:10.2337/dc18-S004.[PubMed 29222375]

American Diabetes Association (ADA). 14. Diabetes care in the hospital: standards of medical care in diabetes-2018. Diabetes Care. 2018e;41(suppl 1):S144-S151. doi: 10.2337/dc18-S014.[PubMed 29222385]

American Diabetes Association (ADA). 12. Children and adolescents: standards of medical care in diabetes-2018. Diabetes Care. 2018f;41(suppl 1):S126-S136. doi: 10.2337/dc18-S012.[PubMed 29222383]

American Diabetes Association (ADA). 6. Glycemic targets: standards of medical care in diabetes-2018. Diabetes Care. 2018g;41(suppl 1):S55-S64. doi: 10.2337/dc18-S006.[PubMed 29222377]

American Diabetes Association (ADA). 9. Cardiovascular disease and risk management: standards of medical care in diabetes-2018. Diabetes Care. 2018h;41(suppl 1): S86-S104. doi: 10.2337/dc18-S009.[PubMed 29222380]

American Diabetes Association (ADA). 5. Prevention or delay of type 2 diabetes: standards of medical care in diabetes-2018. Diabetes Care. 2018i;41(suppl 1):S51-S54. doi: 10.2337/dc18-S005.[PubMed 29222376]

Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52.[PubMed 27060684]

Balani J, Hyer SL, Rodin DA, et al, “Pregnancy Outcomes in Women With Gestational Diabetes Treated With Metformin or Insulin: A Case-Control Study,” Diabet Med, 2009, 26(8):798-802.[PubMed 19709150]

Baptista T, Rangel N, Fernández V, et al. Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: a multicentric, double-blind, placebo-controlled trial. Schizophr Res. 2007;93(1-3):99-108.[PubMed 17490862]

Barbieri R. Metformin for treatment of the polycystic ovary syndrome. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 8, 2018.

Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(11):4227-4249.[PubMed 24194617 ]

Brackett CC. Clarifying metformin’s role and risks in liver dysfunction. J Am Pharm Assoc (2003). 2010;50(3):407-410. doi: 10.1331/JAPhA.2010.08090[PubMed 20452916]

Briggs GG, Ambrose PJ, Nageotte MP, et al, “Excretion of Metformin Into Breast Milk and the Effect on Nursing Infants,” Obstet Gynecol, 2005, 105(6):1437-41.[PubMed 15932841]

Carrizo E, Fernández V, Connell L, et al. Extended release metformin for metabolic control assistance during prolonged clozapine administration: a 14 week, double-blind, parallel group, placebo-controlled study. Schizophr Res. 2009;113(1):19-26.[PubMed 19515536]

Charles B, Norris R, Xiao X, et al, “Population Pharmacokinetics of Metformin in Late Pregnancy,” Ther Drug Monit, 2006, 28(1):67-72.[PubMed 16418696]

Chen CH, Huang MC, Kao CF, et al. Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight: a 24-week, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2013;74(5):e424-e430. doi: 10.4088/JCP.12m08186.[PubMed 23759461]

Coetzee EJ and Jackson WP, “Metformin in Management of Pregnant Insulin-Independent Diabetics,” Diabetologia, 1979, 16(4):241-5.[PubMed 428695]

Coetzee EJ and Jackson WP, “Oral Hypoglycaemics in the First Trimester and Fetal Outcome,” S Afr Med J, 1984, 65(16):635-7.[PubMed 6369573]

Cooper SJ, Reynolds GP, Barnes T, et al. BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment. J Psychopharmacol. 2016;30(8):717-748. doi: 10.1177/0269881116645254.[PubMed 27147592]

Copeland KC, Silverstein J, Moore KR, et al. Management of newly diagnosed type 2 diabetes mellitus (T2DM) in children and adolescents. Pediatrics. 2013;131(2):364-382.[PubMed 23359574]

Corbett S, Shmorgun D, Claman P, Reproductive Endocrinology Infertility Committee, Healey S, Gysler M. The prevention of ovarian hyperstimulation syndrome. J Obstet Gynaecol Can. 2014;36(11):1024-1036.[PubMed 25574681]

Costello M, Shrestha B, Eden J, Sjoblom P, Johnson N. Insulin-sensitising drugs versus the combined oral contraceptive pill for hirsutism, acne and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome. Cochrane Database Syst Rev. 2007;(1):CD005552.[PubMed 17253562]

Crowley MJ, Diamantidis CJ, McDuffie JR, et al. Clinical outcomes of metformin use in populations with chronic kidney disease, congestive heart failure, or chronic liver disease: a systematic review. Ann Intern Med. 2017;166(3):191-200. doi: 10.7326/M16-1901.[PubMed 28055049]

Das C, Mendez G, Jagasia S, Labbate LA. Second-generation antipsychotic use in schizophrenia and associated weight gain: a critical review and meta-analysis of behavioral and pharmacologic treatments. Ann Clin Psychiatry. 2012;24(3):225-239.[PubMed 22860242]

de Oliveira Baraldi C, Lanchote VL, de Jesus Antunes N, et al, “Metformin Pharmacokinetics in Nondiabetic Pregnant Women With Polycystic Ovary Syndrome,” Eur J Clin Pharmacol, 2011, 67(10):1027-33.[PubMed 21538144]

de Silva VA, Suraweera C, Ratnatunga SS, Dayabandara M, Wanniarachchi N, Hanwella R. Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis. BMC Psychiatry. 2016;16(1):341.[PubMed 27716110]

Doldi N, Persico P, Di Sebastiano F, Marsiglio E, Ferrari A. Gonadotropin-releasing hormone antagonist and metformin for treatment of polycystic ovary syndrome patients undergoing in vitro fertilization-embryo transfer. Gynecol Endocrinol. 2006;22(5):235-238.[PubMed 16785142]

Ekpebegh CO, Coetzee EJ, van der Merwe L, et al, “A 10-Year Retrospective Analysis of Pregnancy Outcome in Pregestational Type 2 Diabetes: Comparison of Insulin and Oral Glucose-Lowering Agents,” Diabet Med, 2007, 24(3):253-8.[PubMed 17305787]

Eurich DT, Weir DL, Majumdar SR, et al. Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients. Circ Heart Fail. 2013;6(3):395-402. doi: 10.1161/CIRCHEARTFAILURE.112.000162.[PubMed 23508758]

Eyal S, Easterling TR, Carr D, et al, “Pharmacokinetics of Metformin During Pregnancy,” Drug Metab Dispos, 2010, 38(5):833-40.[PubMed 20118196]

Fauser BC, Tarlatzis BC, Rebar RW, et al, “Consensus on Women’s Health Aspects of Polycystic Ovary Syndrome (PCOS): The Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group,” Fertil Steril, 2012, 97(1):28-38.[PubMed 22153789 ]

Fortamet (metformin) [prescribing information]. Florham Park, NJ: Shionogi; November 2018.

Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2017 executive summary. Endocr Pract. 2017;23(2):207-238. doi: 10.4158/EP161682.CS.[PubMed 28095040]

Gardiner SJ, Kirkpatrick CM, Begg EJ, et al, “Transfer of Metformin Into Human Milk,” Clin Pharmacol Ther, 2003, 73(1):71-7.[PubMed 12545145]

Glucophage (metformin) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; May 2018.

Glucophage (metformin) [product monograph]. Laval, Quebec, Canada: Sanofi-aventis Canada Inc; March 2018.

Glucophage XR (metformin) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; May 2018.

Glumetza (metformin) [prescribing information]. Bridgewater, NJ: Salix Pharmaceuticals; November 2018.

Glumetza (metformin) [product monograph]. Montreal, Quebec, Canada: Valeant Canada; June 2012.

Hale TW, Kristensen JH, Hackett LP, et al, “Transfer of Metformin Into Human Milk,” Diabetologia, 2002, 45(11):1509-14.[PubMed 12436333]

Hughes RC, Gardiner SJ, Begg EJ, et al, “Effect of Pregnancy on the Pharmacokinetics of Metformin,” Diabet Med, 2006, 23(3):323-6.[PubMed 16492218 ]

Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK. Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA. 2014;312(24):2668-2675. doi: 10.1001/jama.2014.15298.[PubMed 25536258]

Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126.[PubMed 10891521]

Jarskog LF, Hamer RM, Catellier DJ, et al; METS Investigators. Metformin for weight loss and metabolic control in overweight outpatients with schizophrenia and schizoaffective disorder. Am J Psychiatry. 2013;170(9):1032-1040. doi:10.1176/appi.ajp.2013.12010127.[PubMed 23846733]

Kancherla V, Elliott JL Jr, Patel BB, et al. Long-term Metformin Therapy and Monitoring for Vitamin B12 Deficiency Among Older Veterans. J Am Geriatr Soc. 2017;65(5):1061-1066.[PubMed 28182265]

Knowler WC, Barrett-Connor E, Fowler SE, et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403.[PubMed 11832527]

Legro RS, Arslanian SA, Ehrmann DA, et al; Endocrine Society. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565-4592.[PubMed 24151290]

Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care. 2011;34(6):1431-1437.[PubMed 21617112]

McCulloch DK. Prevention of type 2 diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 8, 2018a.

McCulloch DK. Initial management of blood glucose in adults with type 2 diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 8, 2018b.

McCulloch DK. Metformin in the treatment of adults with type 2 diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 8, 2018c.

McIntyre RS, Alsuwaidan M, Goldstein BI, et al; Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force. The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force recommendations for the management of patients with mood disorders and comorbid metabolic disorders. Ann Clin Psych. 2012;24(1):69-81.[PubMed 22303523]

Metzger BE, Buchanan TA, Coustan DR, et al, “Summary and Recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus,” Diabetes Care, 2007, 30(Suppl 2):S251-60.[PubMed 17596481]

Mizuno Y, Suzuki T, Nakagawa A, et al. Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. Schizophr Bull. 2014;40(6):1385-1403. doi: 10.1093/schbul/sbu030.[PubMed 24636967]

Moghetti P, Castello R, Negri C, et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab. 2000;85(1):139-146.[PubMed 10634377]

Morin-Papunen L, Vauhkonen I, Koivunen R, Ruokonen A, Martikainen H, Tapanainen JS. Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab. 2003;88(1):148-156.[PubMed 12519844]

Nachum Z, Zafran N, Salim R, et al. Glyburide versus metformin and their combination for the treatment of gestational diabetes mellitus: a randomized controlled study. Diabetes Care. 2017;40(3):332-337. doi: 10.2337/dc16-2307.[PubMed 28077460]

Nathan DM, Buse JB, Davidson MB, et al; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32(1):193-203.[PubMed 18945920]

Nestler JE, Stovall D, Akhter N, Iuorno MJ, Jakubowicz DJ. Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome. Fertil Steril. 2002;77(2):209-215.[PubMed 11821072]

Niromanesh S, Alavi A, Sharbaf FR, Amjadi N, Moosavi S, Akbari S. Metformin compared with insulin in the management of gestational diabetes mellitus: a randomized clinical trial. Diabetes Res Clin Pract. 2012;98(3):422-429.[PubMed 23068960]

Page RL 2nd, O’Bryant CL, Cheng D, et al; American Heart Association Clinical Pharmacology and Heart Failure and Transplantation Committees of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association [published correction appears in Circulation. 2016;134(12):e261]. Circulation. 2016;134(6):e32-e69.[PubMed 27400984]

Palomba S, Falbo A, Carrillo L, et al; METformin in High Responder Italian Group. Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial. Fertil Steril. 2011;96(6):1384-1390.e4.[PubMed 21982727]

Palomba S, Falbo A, La Sala GB. Effects of metformin in women with polycystic ovary syndrome treated with gonadotrophins for in vitro fertilisation and intracytoplasmic sperm injection cycles: a systematic review and meta-analysis of randomised controlled trials. BJOG. 2013;120(3):267-276.[PubMed 23194199]

Practice Committee of the American Society for Reproductive Medicine. Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): a guideline. Fertil Steril. 2017;108(3):426-441. doi:10.1016/j.fertnstert.2017.06.026.[PubMed 28865539]

Rado J, von Ammon Cavanaugh S. A naturalistic randomized placebo-controlled trial of extended-release metformin to prevent weight gain associated with olanzapine in a US community-dwelling population. J Clin Psychopharmacol. 2016;36(2):163-168. doi: 10.1097/JCP.0000000000000469.[PubMed 26872112]

Riomet (metformin) [prescribing information]. Cranbury, NJ: Sun Pharmaceuticals; November 2018.

Rowan JA, Gao W, Hague WM, et al. Glycemia and Its Relationship to Outcomes in the Metformin in Gestational Diabetes Trial,” Diabetes Care, 2010, 33(1):9-16.[PubMed 19846793]

Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes [published correction appears in N Engl J Med. 2008;359(1):106]. N Engl J Med. 2008;358(19):2003-2015.[PubMed 18463376]

Tang T, Glanville J, Orsi N, Barth JH, Balen AH. The use of metformin for women with PCOS undergoing IVF treatment. Hum Reprod. 2006;21(6):1416-1425.[PubMed 16501038]

Teede HJ, Misso ML, Deeks AA, et al. Assessment and management of polycystic ovary syndrome: summary of an evidence-based guideline. Med J Aust. 2011;195(6):S65-112.[PubMed 21929505]

Tertti K, Ekblad U, Koskinen P, Vahlberg T, Rönnemaa T. Metformin vs insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin. Diabetes Obes Metab. 2013;15(3):246-251. doi:10.1111/dom.12017.[PubMed 23020608]

Tertti K, Ekblad U, Vahlberg T, et al, “Comparison of Metformin and Insulin in the Treatment of Gestational Diabetes: A Retrospective, Case-Control Study,” Rev Diabet Stud, 2008, 5(2):95-101.[PubMed 18795211]

Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril. 2008;89(3):505-522. doi:10.1016/j.fertnstert.2007.09.041.[PubMed 18243179]

Tso LO, Costello MF, Albuquerque LE, Andriolo RB, Macedo CR. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2014;11:CD006105.[PubMed 25406011]

Vanky E, Zahlsen K, Spigset O, et al, “Placental Passage of Metformin in Women With Polycystic Ovary Syndrome,” Fertil Steril, 2005, 83(5):1575-8.[PubMed 15866611]

Vause TD, Cheung AP, Sierra S, et al. Ovulation induction in polycystic ovary syndrome: No. 242, May 2010. Int J Gynaecol Obstet. 2010;111(1):95-100. Erratum in:J Obstet Gynaecol Can. 2011;33(1):12.[PubMed 20500959]

Wang M, Tong JH, Zhu G, Liang GM, Yan HF, Wang XZ. Metformin for treatment of antipsychotic-induced weight gain: a randomized, placebo-controlled study. Schizophr Res. 2012;138(1):54-57. doi: 10.1016/j.schres.2012.02.021.[PubMed 22398127]

Zeitler P, Fu J, Tandon N, et al; International Society for Pediatric and Adolescent Diabetes. ISPAD clinical practice consensus guidelines 2014. Type 2 diabetes in the child and adolescent. Pediatr Diabetes. 2014;15(suppl 20):26-46.[PubMed 25182306]

Zhang X, Harmsen WS, Mettler TA, et al. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology. 2014;60(6):2008-2016. doi: 10.1002/hep.27199[PubMed 24798175]

Zheng W, Li XB, Tang YL, Xiang YQ, Wang CY, de Leon J. Metformin for weight gain and metabolic abnormalities associated with antipsychotic treatment: meta-analysis of randomized, placebo-controlled trials. J Clin Psychopharmacol. 2015;35(5):499-509. doi: 10.1097/JCP.0000000000000392.[PubMed 26280837]

Brand Names: International

Adecco (ID); Alexodiab (EG); Amophage (EG); Ansures (MY, PH); Bentic (PY); Biguax (CO); Dabex (MX); Dainipron (HK); Deson (TH); DH-Metglu 850 (VN); DH-Metglu XR 1000 (VN); Diabemet (MY); Diabetase (DE); Diabetmin (HK, MY, SG); Diabetmin Retard (HK); Diabetmin XR (SG); Diabetol (PY); Diabex (AU, KR); Diabex XR (AU); Diafat (PH); Diaformin (BR, HK, TW, UA); Diaformin XR (AU, ID); Diaformina (UY); Diaformina LP (UY); Dialon (AE, BH, KW, LB, QA, SA); Diamet (JO); Dianben (ES); Diaphage (EG, LB); Diaslim (TH); Diformin (FI); Diformin Retard (FI); Dimefor (CO, MX, PE); Dimet (ET); Emnorm (NZ); Euform Retard (PH); Fordica 500 XR (ID); Formet (AU, JO, MY); Formin (BD, IN); Formit (AE, KW, QA, SA); Fornidd (PH); Glafornil (CL); Glibudon (TW); Glicenex (EC); Glicophage (RO); Glifage (BR); Gliformin (CO); Glikos (ID); Glisulin XR (CR, DO, GT, HN, NI, PA, SV); Gluciophage XR (VN); Gluco (TH); Glucodown (KR); Glucofage (EC, VE); Glucofor (ID); Glucoform (PH); Glucogen (KR); Glucoles (TH); Glucomet (ET, SG); Glucomin (IL); Glucomine (TW); Glucon (MY); Glucophage (AE, AR, AT, AU, BB, BE, BF, BH, BJ, BM, BS, BZ, CH, CI, CN, CY, CZ, DK, EE, EG, ET, FI, FR, GB, GH, GM, GN, GR, GY, HK, HR, ID, IE, IN, IQ, IR, IS, IT, JM, JO, KE, KW, LB, LR, LU, LV, LY, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NO, OM, PE, PH, PK, PT, QA, RU, SA, SC, SD, SE, SI, SK, SL, SN, SR, SY, TN, TR, TT, TW, TZ, UA, UG, VN, YE, ZA, ZM, ZW); Glucophage Forte (CZ, NL, PH); Glucophage Retard (EG, IL, QA); Glucophage SR (GB, IE); Glucophage XR (AE, BB, CN, HK, KW, LB, MY); Glucophage-Mite (DE); Glucotika (ID); Glucotin (PH); Gludepatic (ID); Glufor (ID); Glumet (MY, PH); Glumet DC (MY); Glumet Forte (HK); Glumet XR (PH); Glumin (ID); Glumin XR (ID); Glunor (PE); Glupa (KR); Glustress (TH); Glutamet (ET); Glutomin (EG); Glyciphage (IN); Glycomet (SG, UA); Glycomin (KR); Glyformin (TW); Glymet (AE, BH, CY, ET, IQ, IR, JO, KW, LY, OM, QA, SA, SY, YE); Guamet (HK); Heskopaq (ID); Humamet (PH); Humamet XR (PH); I-Max (PH); Indform (VN); Insufor (UA); Insumed (PH); Islotin (AR); Lucomet (IE); Maformin (TH); Medfort (PE); Mefarmil (UA); Meglucon (DE, VN); Melbin (HK, JP); Merckformin (HU); Mescorit (DE); Metaphage (BH); Metchek (NZ); Metdia (VN); Metex XR (AU); Metfar (BD); Metfin (ZW); Metfogamma (DE, LV); Metfor (AE, QA); Metfor XR (PH); Metforal (CR, DO, EC, GT, HN, IT, LT, LV, NI, PA, SG, SV); Metform (BD); Metformax (BE, LU); Metgluco (JP); Metgreen-SR (KR); Metophage (IE); Metta SR (ZW); Miformin (TH); Neoform (PH); Normax (PH); Omformin (BH); Orabet (AT, DK, GB, IE); Panfor SR (PH); Predial (CR, DO, GT, HN, NI, PA, SV); Quexel (CR, DO, EC, GT, HN, NI, PA, SV); Risidon (PT); Siamformet (TH); Siofor (BG, DE, PL, SI, SK); Stagid (PT); Sukkarto SR (GB); Thiabet (DE); Walaphage (IN); Xmet (ET); Yaltormin (IE)

Metformin (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(met FOR min)

Brand Names: US

D-Care DM2 [DSC]; Fortamet; Glucophage; Glucophage XR; Glumetza; Riomet

Brand Names: Canada

Glucophage; Glumetza; Glycon

Warning
  • Rarely, metformin may cause an acid health problem in the blood (lactic acidosis). The risk of lactic acidosis is higher in people with kidney problems and in people who take certain other drugs like topiramate. The risk is also higher in people with liver problems or heart failure, in older people (65 or older), or with alcohol use. The risk is also higher in people who are having an exam or test with contrast, surgery, or other procedures. If lactic acidosis happens, it can lead to other health problems and can be deadly. Lab tests to check the kidneys may be done while taking this drug. If you have questions, talk with the doctor.
  • Do not take this drug if you have a very bad infection, low oxygen, or a lot of fluid loss (dehydration).
  • Call your doctor right away if you have signs of too much lactic acid in the blood (lactic acidosis) like fast breathing, fast or slow heartbeat, a heartbeat that does not feel normal, very bad upset stomach or throwing up, feeling very sleepy, shortness of breath, feeling very tired or weak, very bad dizziness, feeling cold, or muscle pain or cramps.
What is this drug used for?
  • It is used to lower blood sugar in patients with high blood sugar (diabetes).
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to metformin or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Acidic blood problem, kidney disease, or liver disease.
  • If you have had a recent heart attack or stroke.
  • If you are not able to eat or drink like normal, including before certain procedures or surgery.
  • If you are having an exam or test with contrast or have had one within the past 48 hours, talk with your doctor.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Talk with your doctor before you drink alcohol.
  • Do not drive if your blood sugar has been low. There is a greater chance of you having a crash.
  • Check your blood sugar as you have been told by your doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • It may be harder to control your blood sugar during times of stress like when you have a fever, an infection, an injury, or surgery. A change in level of physical activity or exercise and a change in diet may also affect your blood sugar. Talk with your doctor.
  • Follow the diet and workout plan that your doctor told you about.
  • If diarrhea happens or you are throwing up, call your doctor. You will need to drink more fluids to keep from losing too much fluid.
  • Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • There is a chance of pregnancy in women of childbearing age who have not been ovulating. If you want to avoid pregnancy, use birth control that you can trust while taking this drug.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • Extended-release tablets:
  • You may see something that looks like the tablet in your stool. This is normal and not a cause for concern. If you have questions, talk with your doctor.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Very bad belly pain.
  • It is common to have stomach problems like upset stomach, throwing up, or diarrhea when you start taking this drug. If you have stomach problems later during care, call your doctor right away. This may be a sign of an acid health problem in the blood (lactic acidosis).
  • Low blood sugar can happen. The chance of low blood sugar may be raised when this drug is used with other drugs for high blood sugar (diabetes). Signs may be dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating. Call your doctor right away if you have any of these signs. Follow what you have been told to do if you get low blood sugar. This may include taking glucose tablets, liquid glucose, or some fruit juices.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Diarrhea.
  • Gas.
  • Upset stomach or throwing up.
  • Feeling tired or weak.
  • Headache.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Take with meals.
  • Take with a full glass of water.
  • This drug may be used alone or with other high blood sugar (diabetes) drugs.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • Extended-release tablets:
  • Take with the evening meal if taking once daily.
  • Swallow whole. Do not chew, break, or crush.
  • If you have trouble swallowing, talk with your doctor.
  • Liquid (solution):
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
What do I do if I miss a dose?
  • Skip the missed dose and go back to your normal time unless your doctor tells you to do something else.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Metformin (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(met FOR min)

Brand Names: US

D-Care DM2 [DSC]; Fortamet; Glucophage; Glucophage XR; Glumetza; Riomet

Brand Names: Canada

Glucophage; Glumetza; Glycon

Warning
  • Rarely, metformin may cause an acid health problem in the blood (lactic acidosis). The risk of lactic acidosis is higher in people with kidney problems and in people who take certain other drugs like topiramate. The risk is also higher in people with liver problems or heart failure, in older people (65 or older), or with alcohol use. The risk is also higher in people who are having an exam or test with contrast, surgery, or other procedures. If lactic acidosis happens, it can lead to other health problems and can be deadly. Lab tests to check the kidneys may be done while taking this drug. If you have questions, talk with the doctor.
  • Do not give this drug to your child if your child has a very bad infection, low oxygen, or a lot of fluid loss.
  • Call the doctor right away if your child has signs of too much lactic acid in the blood (lactic acidosis) like fast breathing, fast heartbeat, a heartbeat that does not feel normal, very bad upset stomach or throwing up, feeling very sleepy, shortness of breath, feeling very tired or weak, very bad dizziness, feeling cold, or muscle pain or cramps.
What is this drug used for?
  • It is used to lower blood sugar in patients with high blood sugar (diabetes).
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has any of these health problems: Acidic blood problem, kidney disease, or liver disease.
  • If your child has had a recent heart attack or stroke.
  • If your child is not able to eat or drink like normal, including before certain procedures or surgery.
  • If your child is having an exam or test with contrast, or has had one within the past 48 hours, talk with the doctor.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • All products:
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • If your child is old enough to drive, do not let your child drive if his/her blood sugar has been low. There is a greater chance of having a crash.
  • Have your child’s blood sugar checked as you have been told by your child’s doctor.
  • Have your child’s blood work checked often. Talk with your child’s doctor.
  • It may be harder to control your child’s blood sugar during times of stress like when your child has a fever, an infection, an injury, or surgery. A change in level of physical activity or exercise and a change in diet may also affect your child’s blood sugar. Talk with the doctor.
  • Have your child follow the diet and workout plan your child’s doctor told you about.
  • If your child has diarrhea or is throwing up, call your child’s doctor. Your child will need to drink more fluids to keep from losing too much fluid.
  • Have your child be careful in hot weather or while your child is being active. Have your child drink lots of fluids to stop fluid loss.
  • If your child is or may be sexually active:
  • There is a chance of pregnancy in females of childbearing age who have not been ovulating. To avoid pregnancy, have your child use birth control while taking this drug.
  • If your child is pregnant or breast-feeding a baby:
  • Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.
  • Extended-release tablets:
  • You may see something that looks like the tablet in your child’s stool. This is normal and not a cause for concern. If you have questions, talk with your child’s doctor.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Very bad belly pain.
  • It is common to have stomach problems like upset stomach, throwing up, or diarrhea when starting this drug. If your child has stomach problems later during care, call the doctor right away. This may be a sign of an acid health problem in the blood (lactic acidosis).
  • Low blood sugar can happen. The chance of low blood sugar may be raised when this drug is used with other drugs for high blood sugar (diabetes). Signs may be dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating. Call the doctor right away if your child has any of these signs. Follow what you have been told to do if your child gets low blood sugar. This may include giving your child glucose tablets, liquid glucose, or some fruit juices.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Diarrhea.
  • Gas.
  • Upset stomach or throwing up.
  • Feeling tired or weak.
  • Headache.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Give this drug with meals.
  • Give this drug with a full glass of water.
  • This drug may be used alone or with other high blood sugar (diabetes) drugs.
  • To gain the most benefit, do not miss giving your child doses.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • Extended-release tablets:
  • Give with the evening meal if giving once daily.
  • Have your child swallow whole. Do not let your child chew, break, or crush.
  • If your child has trouble swallowing, talk with the doctor.
  • Liquid (solution):
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
What do I do if my child misses a dose?
  • Skip the missed dose and go back to your child’s normal time unless your child’s doctor tells you to do something else.
  • Do not give 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.