Brand name: Glumetza
Drug class: Biguanides

Medically reviewed by Drugs.com on Sep 10, 2025. Written by ASHP.

Introduction

Antidiabetic agent; a biguanide, chemically and pharmacologically unrelated to sulfonylurea antidiabetic agents.

Uses for metFORMIN

Type 2 Diabetes Mellitus

Used as an adjunct to diet and exercise for the management of type 2 diabetes mellitus. Immediate-release tablets and oral solution used in adult and pediatric patients ≥10 years of age; extended-release tablets used in adult patients.

May be used in combination with a glucagon-like peptide-1 (GLP-1) agonist, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, a dipeptidyl peptidase-4 (DPP-4) inhibitor, a thiazolidinedione antidiabetic agent, a sulfonylurea, or a meglitinide (repaglinide, nateglinide) for the management of type 2 diabetes mellitus in patients who do not achieve adequate glycemic control on monotherapy with metformin or any of these medications.

May be used with insulin to improve glycemic control and/or decrease the required dosage of insulin.

Commercially available in fixed combination with glyburide or glipizide for use as an adjunct to diet and exercise in adults with type 2 diabetes mellitus.

Commercially available in fixed combination with pioglitazone for use as an adjunct to diet and exercise in adult patients with type 2 diabetes mellitus who have inadequate glycemic control with pioglitazone or metformin monotherapy or in those who are already receiving pioglitazone and metformin concurrently as separate components.

Commercially available in fixed combination with the DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, or sitagliptin for use in adult patients as an adjunct to diet and exercise when treatment with both medication components is appropriate.

Commercially available in fixed combinations with the SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin in adult and pediatric patients ≥10 years of age and with ertugliflozin for use in adults when treatment with both medication components is appropriate.

Guidelines from the American Diabetes Association (ADA) and other experts recommend metformin for those patients that require initiation or intensification of glucose-lowering therapy to meet glycemic goals and do not have additional needs beyond glucose lowering and for add-on therapy to maintain HbA_1c goals. When selecting a treatment regimen, consider factors such as cardiovascular and renal comorbidities, drug efficacy and adverse effects, hypoglycemic risk, presence of overweight or obesity, cost, access, and patient preferences. Weight management should be included as a distinct treatment goal and other healthy lifestyle behaviors should also be considered.

Polycystic Ovary Syndrome

Has been used in the management of metabolic and reproductive abnormalities associated with polycystic ovary syndrome^{† [off-label]}.

metFORMIN Dosage and Administration

General

Pretreatment Monitoring

• Assess renal function.

• Assess hematologic parameters and vitamin B₁₂ concentration.

Patient Monitoring

• Monitor hematologic parameters on an annual basis and vitamin B₁₂ at 2- to 3-year intervals. Replete vitamin B₁₂as appropriate.

• Assess renal function (i.e., estimated glomerular filtration rate [eGFR]) at least annually; assess more frequently in patients at risk for development of renal impairment (e.g., geriatric patients).

• Monitor with regular laboratory evaluations, including blood glucose determinations, to assess therapeutic response and to determine minimum effective dosage. Glycosylated hemoglobin (hemoglobin A_1c [HbA_1c]) measurements are also useful, particularly for long-term control of blood glucose concentrations.

• Following initiation and dosage titration, determination of HbA_1c concentrations at intervals of approximately 3 months is useful for assessing patient's continued response to therapy.

Dispensing and Administration Precautions

• The Institute for Safe Medication Practices (ISMP) includes metFORMIN and metroNIDAZOLE on the ISMP List of Confused Drug Names, and recommends special safeguards to ensure the accuracy of prescriptions for these medications.

Other General Considerations

• Discontinue at the time of, or prior to, an iodinated procedure in patients with an eGFR 30—60 mL/minute per 1.73 m²; in patients with a history of liver disease, alcohol use disorder, or heart failure; or in patients who will be administered intraarterial contrast. Assess eGFR 48 hours after the imaging procedure and restart if renal function is stable.

• Discontinue temporarily in patients who require restricted food and fluid intake during surgical or other procedures, as this may increase the risk for volume depletion, hypotension, and renal impairment.

Administration

Oral Administration

Administer orally with meals to reduce adverse GI effects.

Administer immediate-release tablets in 2 divided doses daily if total dosage ≤2 g daily or in 3 divided doses daily if total dosage is >2 g daily.

Administer oral solution either once or twice daily with meals. Dosages >2 g daily may be better tolerated if administered in 3 divided doses daily. Measure each dose using a specific dosing cup.

Administer extended-release tablets once daily with the evening meal; swallow whole and do not chew, cut, or crush.

Administer immediate-release metformin hydrochloride in fixed combination with canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, glipizide, glyburide, pioglitazone, alogliptin, linagliptin, or sitagliptin in divided doses daily with meals to reduce the GI effects of the metformin hydrochloride component. See full prescribing information for additional administration instructions for combination products.

Administer extended-release metformin hydrochloride in fixed combination with canagliflozin, dapagliflozin, or empagliflozin once daily with the morning meal. See full prescribing information for additional administration instructions for combination products.

Administer the fixed combination of extended-release metformin hydrochloride and linagliptin once daily with a meal. Administer the fixed combination of extended-release metformin hydrochloride and sitagliptin once daily with a meal, preferably the evening meal. Administer extended-release metformin hydrochloride in fixed combination with saxagliptin once daily with the evening meal. See full prescribing information for additional administration instructions for combination products.

Dosage

Available as metformin hydrochloride; dosage expressed in terms of the salt.

Individualize dosage carefully based on patient’s glycemic response and tolerance.

Pediatric Patients

Type 2 Diabetes Mellitus

Metformin Hydrochloride Monotherapy

Oral

Immediate-release tablets or immediate-release oral solution in children or adolescents ≥10 years of age: Initially, 500 mg twice daily with meals.

Increase daily dosage in increments of 500 mg at weekly intervals to a maximum of 2 g daily given in 2 divided doses.

Immediate-release Metformin Hydrochloride in Fixed Combination with Canagliflozin (Invokamet)

Oral

Individualize dosage based on patient's current antidiabetic regimen. May increase dosage gradually based on effectiveness and tolerability.

Children or adolescents ≥10 years of age not currently receiving either metformin hydrochloride or canagliflozin: Initially, 500 mg of metformin hydrochloride and 50 mg of canagliflozin twice daily.

Children or adolescents ≥10 years of age currently receiving metformin hydrochloride: Initially, a total daily metformin hydrochloride dosage similar to the patient's existing dosage and 100 mg of canagliflozin, administered in 2 divided doses. In patients currently receiving an evening dose of extended-release metformin hydrochloride, skip last dose of extended-release metformin hydrochloride prior to initiating therapy with the fixed combination of metformin hydrochloride and canagliflozin the following morning.

Children or adolescents ≥10 years of age currently receiving canagliflozin: Initially, 1 g of metformin hydrochloride and same daily dosage of canagliflozin administered in 2 divided doses.

Children or adolescents ≥10 years of age currently receiving metformin hydrochloride and canagliflozin: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and same daily dosage of canagliflozin, administered in 2 divided doses.

Extended-release Metformin Hydrochloride in Fixed Combination with Canagliflozin (Invokamet XR)

Oral

Individualize dosage based on patient's current antidiabetic regimen. May increase dosage gradually based on effectiveness and tolerability.

Children or adolescents ≥10 years of age not currently receiving either metformin hydrochloride or canagliflozin: Initially, 1 g of metformin hydrochloride and 100 mg of canagliflozin once daily.

Children or adolescents ≥10 years of age currently receiving metformin hydrochloride: Initially, a total daily metformin hydrochloride dosage similar to the patient's existing dosage and 100 mg of canagliflozin, administered once daily. In patients currently receiving an evening dose of extended-release metformin hydrochloride, skip last dose of extended-release metformin hydrochloride prior to initiating therapy with the fixed combination of metformin hydrochloride and canagliflozin the following morning.

Children or adolescents ≥10 years of age currently receiving canagliflozin: Initially, 1 g of metformin hydrochloride and same daily dosage of canagliflozin administered once daily.

Children or adolescents ≥10 years of age currently receiving metformin hydrochloride and canagliflozin: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and same daily dosage of canagliflozin, administered once daily.

Extended-release Metformin Hydrochloride in Fixed Combination with Dapagliflozin (Xigduo XR)

Oral

Initial dosage based on patient's current regimen with metformin hydrochloride and/or dapagliflozin. May increase dosage gradually based on effectiveness and tolerability.

Children or adolescents ≥10 years of age not currently receiving metformin and/or dapagliflozin: Initially, 500 mg of the extended-release metformin component and 5 mg of the dapagliflozin component once daily. Titrate gradually based on effectiveness and tolerability, up to a maximum daily dosage of 2 g of extended-release metformin and 10 mg of dapagliflozin.

Children or adolescents ≥10 years of age already receiving extended-release metformin hydrochloride in the evening who are switching to the fixed combination of metformin hydrochloride and dapagliflozin: Skip last dose of metformin hydrochloride before initiating therapy with the fixed combination the following morning.

Immediate-release Metformin Hydrochloride in Fixed Combination with Empagliflozin (Synjardy)

Oral

Individualize dosage based on the patient's current antidiabetic regimen. May increase dosage gradually based on effectiveness and tolerability.

Children or adolescents ≥10 years of age currently receiving metformin hydrochloride: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and 10 mg of empagliflozin, administered in 2 divided doses.

Children or adolescents ≥10 years of age currently receiving empagliflozin: Initially, 1 g of metformin hydrochloride and same daily dosage of empagliflozin administered in 2 divided doses.

Children or adolescents ≥10 years of age currently receiving metformin hydrochloride and empagliflozin: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and same daily dosage of empagliflozin, administered in 2 divided doses.

Extended-release Metformin Hydrochloride in Fixed Combination with Empagliflozin (Synjardy)

Oral

Individualize dosage based on the patient's current antidiabetic regimen. May increase dosage gradually based on effectiveness and tolerability.

Children or adolescents ≥10 years of age currently receiving metformin hydrochloride: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and 10 mg of empagliflozin, administered once daily.

Children or adolescents ≥10 years of age currently receiving empagliflozin: Initially, 1 g of metformin hydrochloride and same daily dosage of empagliflozin administered once daily.

Children or adolescents ≥10 years of age currently receiving metformin hydrochloride and empagliflozin: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and same daily dosage of empagliflozin, administered once daily.

Adults

Type 2 Diabetes Mellitus

Metformin Hydrochloride Monotherapy

Oral

Immediate-release tablets or immediate-release oral solution: Initially, 500 mg twice daily or 850 mg once daily with meals.

Increase daily dosage by 500 mg at weekly intervals or by 850 mg at biweekly (every 2 week) intervals up to a maximum of 2.55 g daily given in divided doses.

Clinically important responses generally not observed at dosages <1.5 g daily.

Extended-release tablets: Initially, 500 mg once daily with the evening meal. Increase daily dosage by 500 mg at weekly intervals or every 1 to 2 weeks based on glycemic control and tolerability up to a maximum of 2 g daily. If glycemic control is not achieved with 2 g once daily, consider administering 1 g twice daily. If >2 g daily is required, switch to immediate-release tablet formulation and increase dosage up to 2.55 g daily in divided doses (preferably 3 doses per day for daily dosages >2 g).

May switch from immediate-release to extended-release metformin hydrochloride tablets at the same total daily dosage, up to 2 g once daily. Following a switch from immediate-release to extended-release metformin, closely monitor glycemic control and adjust dosage accordingly.

Immediate-release Metformin Hydrochloride in Fixed Combination with Glipizide

Oral

Patients with inadequate glycemic control on diet and exercise alone: Initially, 250 mg of metformin hydrochloride and 2.5 mg of glipizide once daily with a meal. For more severe hyperglycemia (fasting plasma glucose concentrations of 280–320 mg/dL), consider 500 mg of metformin hydrochloride and 2.5 mg of glipizide twice daily. Increase daily dosage in increments of one tablet (using the tablet strength at which therapy was initiated) at 2-week intervals until adequate glycemic control is achieved or maximum daily dosage of 1 or 2 g of metformin hydrochloride and 10 mg of glipizide in divided doses is reached.

Efficacy of metformin hydrochloride and glipizide in fixed combination not established in patients with fasting plasma glucose concentrations >320 mg/dL. No experience with total daily dosages exceeding 2 g of metformin hydrochloride and 10 mg of glipizide as initial therapy.

Patients with inadequate glycemic control on either a sulfonylurea or metformin alone: Initially, 500 mg of metformin hydrochloride and 2.5 or 5 mg of glipizide twice daily with the morning and evening meals. Initial dosage of the fixed combination should not exceed the patient's current daily dosage of metformin hydrochloride or glipizide (or equivalent dosage of another sulfonylurea). Titrate daily dosage in increments not exceeding 500 mg of metformin hydrochloride and 5 mg of glipizide until adequate glycemic control achieved or maximum daily dosage of 2 g of metformin hydrochloride and 20 mg of glipizide is reached.

Patients currently receiving combined therapy with separate metformin and glipizide (or another sulfonylurea) preparations: May switch to 500 mg of metformin hydrochloride and 2.5 or 5 mg of glipizide; initial dosage of the fixed-combination preparation should not exceed the patient's current daily dosage of metformin hydrochloride and glipizide (or equivalent dosage of another sulfonylurea). Use clinical judgment regarding whether to switch to the nearest equivalent dosage or to titrate dosage. Titrate daily dosage in increments not exceeding 500 mg of metformin hydrochloride and 5 mg of glipizide until adequate glycemic control is achieved or maximum daily dosage of 2 g of metformin hydrochloride and 20 mg of glipizide is reached.

Immediate-release Metformin Hydrochloride in Fixed Combination with Glyburide

Oral

Patients not already receiving either metformin hydrochloride or glyburide (or another sulfonylurea): Initially, 250 mg of metformin hydrochloride and 1.25 mg of glyburide once or twice daily with meals. Titrate daily dosage gradually based on glycemic control and tolerability up to a maximum daily dosage of 2 g of metformin hydrochloride and 20 mg of glyburide.

Patients with inadequate glycemic control on either glyburide (or another sulfonylurea) or metformin hydrochloride monotherapy: Initially, 500 mg of metformin hydrochloride and 2.5 mg of glyburide or 500 mg of metformin hydrochloride and 5 mg of glyburide twice daily with meals. Increase daily dosage gradually based on glycemic control and tolerability up to a maximum daily dosage of 2 g of metformin hydrochloride and 20 mg of glyburide.

Patients with inadequate glycemic control on the combination of metformin and a sulfonylurea: Initial dosage of the fixed combination should not exceed the patient's current daily dosage of metformin hydrochloride and glyburide (or equivalent dosage of another sulfonylurea antidiabetic agent). Increase daily dosage gradually based on glycemic control and tolerability up to a maximum daily dosage of 2 g of metformin hydrochloride and 20 mg of glyburide.

Immediate-release Metformin Hydrochloride in Fixed Combination with Pioglitazone (Actoplus Met)

Oral

Individualize dosage based on the patient’s current dosage regimen, effectiveness, and tolerability.

Patients in whom combination therapy with metformin and pioglitazone considered appropriate: Initially, 850 mg of metformin hydrochloride and 15 mg of pioglitazone once daily.

Patients inadequately controlled on metformin monotherapy: Initially, 850 mg of metformin hydrochloride and 15 mg of pioglitazone once or twice daily (depending on metformin hydrochloride dosage already being taken).

Patients inadequately controlled on pioglitazone monotherapy: Initially, 850 mg of metformin hydrochloride and 15 mg of pioglitazone once daily.

Patients switching from combination therapy with metformin hydrochloride and pioglitazone given as separate tablets: Use dosage of the fixed combination as close as possible to dosages of metformin hydrochloride and pioglitazone already being taken.

Patients with NYHA class I or II congestive heart failure: Initially, 850 mg of metformin hydrochloride and 15 mg of pioglitazone once daily. Initiation of the fixed combination in patients with NYHA class III or IV congestive heart failure contraindicated.

Gradually titrate dosage as needed based on therapeutic response and tolerability to maximum daily dosage of 2.55 g of metformin hydrochloride and 45 mg of pioglitazone. Metformin hydrochloride dosages >2 g daily may be better tolerated if given in 3 divided doses daily.

Immediate-release Metformin Hydrochloride in Fixed Combination with Alogliptin (Kazano)

Oral

Individualize dosage based on current antidiabetic regimen, effectiveness, and patient tolerability. Increase dosage gradually to minimize adverse GI effects, up to a maximum daily dosage of 2 g of metformin hydrochloride and 25 mg of alogliptin.

Immediate-release Metformin Hydrochloride in Fixed Combination with Linagliptin (Jentadueto)

Oral

Individualize dosage based on effectiveness and patient tolerability. May increase dosage up to a maximum daily dosage of 2 g of metformin hydrochloride and 5 mg of linagliptin.

Patients not currently receiving metformin hydrochloride: Initially, 1 g of metformin hydrochloride and 5 mg of linagliptin administered in 2 divided doses.

Patients currently receiving metformin hydrochloride: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and 5 mg of linagliptin, administered in 2 divided doses.

Patients currently receiving metformin hydrochloride and linagliptin: Initially, same total daily dosage of each component administered in 2 divided doses daily.

Extended-release Metformin Hydrochloride in Fixed Combination with Linagliptin (Jentadueto XR)

Oral

Individualize dosage based on effectiveness and patient tolerability. May increase dosage up to a maximum daily dosage of 2 g of metformin hydrochloride and 5 mg of linagliptin.

Patients not currently receiving metformin hydrochloride: Initially, 1 g of metformin hydrochloride and 5 mg of linagliptin once daily.

Patients currently receiving metformin hydrochloride: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and 5 mg of linagliptin, administered once daily.

Patients currently receiving metformin hydrochloride and linagliptin: Initially, same total daily dosage of each component, administered once daily.

Extended-release Metformin Hydrochloride in Fixed Combination with Saxagliptin (Kombiglyze XR)

Oral

Individualize dosage based on current antidiabetic regimen, clinical response, and tolerability.

Patients who need 5 mg of saxagliptin and who are not currently treated with metformin: Initially, 500 mg of extended-release metformin hydrochloride and 5 mg of saxagliptin once daily; gradually increase dosage to reduce adverse GI effects of metformin.

Patients treated with metformin, the recommended starting dosage of the fixed-combination preparation should provide metformin at the dose already being taken, or the nearest therapeutically appropriate dose. Following a switch from immediate-release to extended-release metformin, monitor glycemic control closely and make dosage adjustments accordingly.

Patients who need saxagliptin 2.5 mg daily in combination with metformin extended-release: 1 g of extended-release metformin hydrochloride and 2.5 mg of saxagliptin daily. Patients who require 2.5 mg of saxagliptin who are either metformin naïve or require a dose of metformin hydrochloride exceeding 1 g should use the individual components.

Maximum recommended dosages of extended-release metformin hydrochloride and saxagliptin in fixed combination are 2 g of extended-release metformin hydrochloride and 5 mg of saxagliptin daily.

When the fixed-combination preparation containing extended-release metformin hydrochloride and saxagliptin is used concomitantly with a potent cytochrome P-450 isoenzyme 3A4/5 (CYP3A4/5) inhibitor, limit dosage of saxagliptin to 2.5 mg once daily.

Immediate-release Metformin Hydrochloride in Fixed Combination with Sitagliptin (Janumet)

Oral

Patients not currently receiving metformin hydrochloride: Initially, 500 mg of metformin hydrochloride and 50 mg of sitagliptin twice daily.

Patients currently receiving metformin hydrochloride: Initially, 500 mg of metformin hydrochloride and 50 mg of sitagliptin twice daily or 1 g of metformin hydrochloride and 50 mg of sitagliptin twice daily, depending on the patient's existing dosage of metformin hydrochloride.

Patients currently receiving immediate-release metformin hydrochloride 850 or 1000 mg twice daily: 1 g of metformin hydrochloride and 50 mg of sitagliptin twice daily.

Maintain the same total daily dosage of sitagliptin and metformin hydrochloride when transitioning between the fixed combination of sitagliptin and immediate-release metformin hydrochloride (Janumet) and the fixed combination of sitagliptin and extended-release metformin hydrochloride (Janumet XR).

Efficacy and safety of switching therapy from oral antidiabetic agents other than metformin hydrochloride or sitagliptin to the fixed combination of sitagliptin and metformin hydrochloride not established.

Extended-release Metformin Hydrochloride in Fixed Combination with Sitagliptin (Janumet XR)

Oral

Patients not currently receiving metformin hydrochloride: Initially, 1 g of metformin hydrochloride and 100 mg of sitagliptin once daily.

Patients currently receiving metformin hydrochloride: Initially, 1 g of metformin hydrochloride and 100 mg of sitagliptin once daily or 2 g of metformin hydrochloride and 100 mg of sitagliptin once daily, depending on the patient's existing dosage of metformin hydrochloride.

Patients currently receiving immediate-release metformin hydrochloride 850 or 1000 mg twice daily: 2 g of metformin hydrochloride and 100 mg of sitagliptin once daily.

Maintain the same total daily dosage of metformin hydrochloride and sitagliptin when transitioning between the fixed combination of sitagliptin and immediate-release metformin hydrochloride and sitagliptin (Janumet) and the fixed combination of extended-release metformin hydrochloride and sitagliptin (Janumet XR).

Efficacy and safety of switching therapy from oral antidiabetic agents other than metformin hydrochloride or sitagliptin to the fixed combination of metformin hydrochloride and sitagliptin not established.

Immediate-release Metformin Hydrochloride in Fixed Combination with Canagliflozin (Invokamet)

Oral

Individualize dosage based on patient's current antidiabetic regimen. May increase dosage gradually based on effectiveness and tolerability.

Patients not currently receiving either metformin hydrochloride or canagliflozin: Initially, 500 mg of metformin hydrochloride and 50 mg of canagliflozin twice daily.

Patients currently receiving metformin hydrochloride: Initially, a total daily metformin hydrochloride dosage similar to the patient's existing dosage and 100 mg of canagliflozin, administered in 2 divided doses. In patients currently receiving an evening dose of extended-release metformin hydrochloride, skip last dose of extended-release metformin hydrochloride prior to initiating therapy with the fixed combination of metformin hydrochloride and canagliflozin the following morning.

Patients currently receiving canagliflozin: Initially, 1 g of metformin hydrochloride and same daily dosage of canagliflozin administered in 2 divided doses.

Patients currently receiving metformin hydrochloride and canagliflozin: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and same daily dosage of canagliflozin, administered in 2 divided doses.

Extended-release Metformin Hydrochloride in Fixed Combination with Canagliflozin (Invokamet XR)

Oral

Individualize dosage based on patient's current antidiabetic regimen. May increase dosage gradually based on effectiveness and tolerability.

Patients not currently receiving either metformin hydrochloride or canagliflozin: Initially, 1 g of metformin hydrochloride and 100 mg of canagliflozin once daily.

Patients currently receiving metformin hydrochloride: Initially, a total daily metformin hydrochloride dosage similar to the patient's existing dosage and 100 mg of canagliflozin, administered once daily. In patients currently receiving an evening dose of extended-release metformin hydrochloride, skip last dose of extended-release metformin hydrochloride prior to initiating therapy with the fixed combination of metformin hydrochloride and canagliflozin the following morning.

Patients currently receiving canagliflozin: Initially, 1 g of metformin hydrochloride and same daily dosage of canagliflozin administered once daily.

Patients currently receiving metformin hydrochloride and canagliflozin: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and same daily dosage of canagliflozin, administered once daily.

Extended-release Metformin Hydrochloride in Fixed Combination with Dapagliflozin (Xigduo XR)

Oral

Initial dosage based on patient's current regimen with metformin hydrochloride and/or dapagliflozin. May increase dosage gradually based on effectiveness and tolerability.

Patients not currently receiving metformin and/or dapagliflozin: Initially, 500 mg of the extended-release metformin component and 5 mg of the dapagliflozin component once daily. Titrate gradually based on effectiveness and tolerability, up to a maximum daily dosage of 2 g of extended-release metformin and 10 mg of dapagliflozin.

Patients already receiving extended-release metformin hydrochloride in the evening who are switching to the fixed combination of metformin hydrochloride and dapagliflozin: Skip last dose of metformin hydrochloride before initiating therapy with the fixed combination the following morning.

Immediate-release Metformin Hydrochloride in Fixed Combination with Empagliflozin (Synjardy)

Oral

Individualize dosage based on the patient's current antidiabetic regimen. May increase dosage gradually based on effectiveness and tolerability.

Patients currently receiving metformin hydrochloride: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and 10 mg of empagliflozin, administered in 2 divided doses.

Patients currently receiving empagliflozin: Initially, 1 g of metformin hydrochloride and same daily dosage of empagliflozin administered in 2 divided doses.

Patients currently receiving metformin hydrochloride and empagliflozin: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and same daily dosage of empagliflozin, administered in 2 divided doses.

Extended-release Metformin Hydrochloride in Fixed Combination with Empagliflozin (Synjardy XR)

Oral

Individualize dosage based on the patient's current antidiabetic regimen. May increase dosage gradually based on effectiveness and tolerability.

Patients currently receiving metformin hydrochloride: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and 10 mg of empagliflozin, administered once daily.

Patients currently receiving empagliflozin: Initially, 1 g of metformin hydrochloride and same daily dosage of empagliflozin administered once daily.

Patients currently receiving metformin hydrochloride and empagliflozin: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and same daily dosage of empagliflozin, administered once daily.

Immediate-release Metformin Hydrochloride in Fixed Combination with Ertugliflozin (Segluromet)

Oral

Initial dosage based on patient's current regimen with metformin hydrochloride and/or ertugliflozin. May increase dosage gradually based on effectiveness and tolerability.

Patients currently receiving metformin hydrochloride: Initially, total daily metformin hydrochloride dosage similar to patient's existing dosage and total daily dosage of 5 mg of ertugliflozin (administered as fixed combination with 2.5 mg of ertugliflozin), given in 2 divided doses daily.

Patients currently receiving ertugliflozin: Initially, total daily dosage of 1 g of metformin hydrochloride (administered as fixed combination with 500 mg of metformin hydrochloride) and the same daily dosage of ertugliflozin , given in 2 divided doses daily.

Patients currently receiving metformin hydrochloride and ertugliflozin (administered as separate tablets): Initially, give fixed combination containing a total daily metformin hydrochloride dosage similar to patient's existing dosage and same total daily dose of ertugliflozin, in 2 divided doses daily.

Polycystic Ovary Syndrome† [off-label]

Oral

In general, 1.5–2.25 g daily in divided doses.

Special Populations

Renal Impairment

Metformin Hydrochloride Monotherapy

eGFR 30–45 mL/minute per 1.73 m²: Initiation of therapy not recommended; assess benefits and risks of continued treatment if eGFR falls below 45 mL/minute per 1.73 m² in patients already receiving metformin.

eGFR <30 mL/minute per 1.73 m²: Contraindicated; discontinue in patients already receiving metformin.

Metformin Hydrochloride in Fixed Combination with Glipizide

eGFR 30–45 mL/minute per 1.73 m²: Initiation of therapy not recommended; assess benefits and risks of continued treatment if eGFR falls below 45 mL/minute per 1.73 m².

eGFR <30 mL/minute per 1.73 m²: Contraindicated; discontinue use in patients already receiving.

Metformin Hydrochloride in Fixed Combination with Glyburide

eGFR 30–45 mL/minute per 1.73 m²: Initiation of therapy not recommended; assess benefits and risks of continued treatment if eGFR falls below 45 mL/minute per 1.73 m².

eGFR <30 mL/minute per 1.73 m²: Contraindicated; discontinue use in patients already receiving.

Metformin Hydrochloride in Fixed Combination with Pioglitazone

eGFR 30–45 mL/minute per 1.73 m²: Initiation of therapy not recommended; assess benefits and risks of continued treatment if eGFR falls below 45 mL/minute per 1.73 m².

eGFR <30 mL/minute per 1.73 m²: Contraindicated; discontinue use in patients already receiving.

Metformin Hydrochloride in Fixed Combination with Alogliptin

eGFR ≥60 mL/minute per 1.73 m²: No dosage adjustment necessary.

eGFR 30—59 mL/minute per 1.73 m²: Use not recommended.

eGFR <30 mL/minute per 1.73 m²: Contraindicated.

Metformin Hydrochloride in Fixed Combination with Linagliptin

eGFR 30–45 mL/minute per 1.73 m²: Initiation of therapy not recommended; assess benefits and risks of continued treatment if eGFR falls below 45 mL/minute per 1.73 m².

eGFR <30 mL/minute per 1.73 m²: Contraindicated; discontinue use in patients already receiving.

Metformin Hydrochloride in Fixed Combination with Saxagliptin

eGFR ≥45 mL/minute per 1.73 m²: No dosage adjustment necessary.

eGFR 30— <45 mL/minute per 1.73 m²: Initiation of therapy not recommended. Assess benefits and risks of continued treatment if eGFR falls below 45 mL/minute per 1.73 m².

eGFR <30 mL/minute per 1.73 m²: Contraindicated; discontinue use in patients already receiving.

Metformin Hydrochloride in Fixed Combination with Sitagliptin

eGFR 30—45 mL/minute per 1.73 m², immediate-releasemetformin hydrochloride: Use not recommended.

eGFR 30—45 mL/minute per 1.73 m², extended-release metformin hydrochloride: Initiation of therapy not recommended. Assess benefits and risks of continued treatment if eGFR falls below 45 mL/minute per 1.73 m².

eGFR <30 mL/minute per 1.73 m², immediate-release metformin hydrochloride: Contraindicated.

eGFR <30 mL/minute per 1.73 m², extended-release metformin hydrochloride: Contraindicated; discontinue use in patients already receiving.

Metformin Hydrochloride in Fixed Combination with Canagliflozin

eGFR 45 to <60 mL/minute per 1.73 m²: Maximum daily dosage of 100 mg of canagliflozin component.

eGFR <45 mL/minute per 1.73 m²: Initiation of therapy not recommended. Assess benefits and risks of continued treatment if eGFR falls below 45 mL/minute per 1.73 m² and do not exceed a maximum daily dosage of 100 mg of canagliflozin component.

eGFR <30 mL/minute per 1.73 m²: Contraindicated; discontinue use in patients already receiving.

Metformin Hydrochloride in Fixed Combination with Dapagliflozin

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

eGFR 30—45 mL/minute per 1.73 m²: Initiation of therapy not recommended. Assess benefits and risks of continued treatment if eGFR falls below 45 mL/minute per 1.73 m².

eGFR <30 mL/minute per 1.73 m²: Contraindicated; discontinue use in patients already receiving.

Metformin Hydrochloride in Fixed Combination with Empagliflozin

eGFR <45 mL/minute per 1.73 m²: Initiation of therapy not recommended.

eGFR <30 mL/minute per 1.73 m²: Contraindicated.

Metformin Hydrochloride in Fixed Combination with Ertugliflozin

eGFR <45 mL/minute per 1.73 m²: Use not recommended.

eGFR <30 mL/minute per 1.73 m², end stage-renal disease, dialysis: Contraindicated.

Hepatic Impairment

Avoid use in those with clinical or laboratory evidence of hepatic disease.

Geriatric Patients

In general, initiate therapy on the lower end of the dosing range and do not titrate to the maximum dosage recommended for younger adults; limited data suggest reducing initial dosage by approximately 33% in geriatric patients.

Monitor renal function more frequently to determine appropriate dosage.

Cautions for metFORMIN

Contraindications

• Acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma.

• Severe renal impairment (eGFR <30 mL/minute per 1.73 m²).

• Hypersensitivity to metformin hydrochloride.

Warnings/Precautions

Warnings

Lactic Acidosis

Lactic acidosis resulting in death, hypothermia, hypotension, and resistant bradyarrhythmias reported (see Boxed Warning). Onset often subtle and may be accompanied by only nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific and unexplained abdominal distress with nausea and vomiting or diarrhea. Characterized by elevated blood lactate concentrations (exceeding 45 mg/dL), anion gap acidosis (without evidence of ketonuria or ketonemia), and increased lactate/pyruvate ratio. Risk appears to increase with degree of renal impairment and patient's age; risk can be minimized by periodic monitoring of renal function and cautious dosage selection. Other risk factors include concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age ≥65 years, undergoing radiological procedures with intravascular contrast agents, surgery and other procedures, hypoxic states, excessive alcohol consumption, and hepatic impairment.

Lactic acidosis constitutes a medical emergency requiring immediate clinician evaluation; in such cases, metformin should be discontinued and general supportive therapy (e.g., volume expansion, diuresis) initiated immediately. Hemodialysis also recommended.

Withhold therapy promptly in patients with any condition associated with hypoxemia, sepsis, or dehydration, or in any patient who becomes acutely unwell. Avoid use in patients with clinical or laboratory evidence of hepatic impairment. Discontinue before or at the time of intravascular iodinated contrast imaging procedures in patients with an eGFR 30—60 mL/minute per 1.73 m² history of liver disease, alcohol use disorder, or heart failure. Evaluate renal function 48 hours after imaging procedure and reinstitute therapy if renal function stable. Withhold temporarily in patients undergoing surgery.

Educate patients of the importance of lactic acid symptoms (e.g., malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific and unexplained abdominal distress with nausea and vomiting or diarrhea) and instruct patients to notify their clinician immediately if these symptoms occur. Advise patients to avoid excessive alcohol intake.

Other Warnings and Precautions

Vitamin B12 Deficiency

Decreased serum vitamin B₁₂ concentrations, with or without clinical manifestations (e.g., anemia). Some patients (i.e., those with an inadequate absorption or intake of vitamin B₁₂ or calcium) appear to be predisposed.

Symptoms rapidly reversible following discontinuation of metformin or supplementation with vitamin B₁₂. Monitor hematologic parameters (e.g., hemoglobin, serum vitamin B₁₂ concentrations) prior to initiation of therapy and at least annually during treatment..

Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues

Metformin may increase the risk of hypoglycemia when combined with insulin or an insulin secretagogues. A lower dosage of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia.

Macrovascular Outcomes

No conclusive evidence of macrovascular risk reduction with metformin.

Use of Fixed Combinations

When used in fixed combination with other medications consider the cautions, precautions, contraindications, and drug interactions associated with the concomitant agent(s) in addition to metformin.

Specific Populations

Pregnancy

Insufficient evidence to determine a medication-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; available studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes. Limited data from uncontrolled or retrospective studies are conflicting regarding long-term maternal therapy on neonatal morbidity (e.g., congenital malformations) and mortality.

Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications and increases fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.

Most clinicians recommend use of insulin during pregnancy in diabetic patients to maintain optimum control of blood glucose concentrations.

Lactation

Distributed into milk in rats; distributed into human milk. Insufficient information to determine effects on breast-fed infant and no available information on effects on milk production.

Consider developmental and health benefits of breastfeeding along with mother's clinical need for the medication and potential adverse effects on breast-fed child (e.g., hypoglycemia). Monitor breastfed infants for signs of hypoglycemia (e.g., jitters, cyanosis, apnea, hypothermia, excessive sleepiness, poor feeding, seizures).

Females and Males of Reproductive Potential

Potential for unplanned pregnancy should be discussed with premenopausal females since metformin-containing therapy may result in ovulation in some anovulatory females.

Pediatric Use

Safety and efficacy of metformin as immediate-release tablets or immediate-release oral solution established in pediatric patients 10—16 years of age; not established in children <10 years of age.

Safety and efficacy of metformin as extended-release tablets in children <17 years of age have not been established.

Geriatric Use

Insufficient number of geriatric patients in controlled clinical trials of metformin hydrochloride immediate-release and extended-release tablets to determine if such patients respond differently than younger adults.

Start at the low end of the dosage range in geriatric patients, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other medication therapy and higher risk of lactic acidosis. Such patients generally should not receive the maximum recommended dosage.

Monitor renal function more frequently.

Hepatic Impairment

Generally avoid use in patients with clinical or laboratory evidence of hepatic disease. Elimination of lactate may be substantially reduced.

Renal Impairment

Substantially excreted renally; risk of accumulation and lactic acidosis increases with degree of renal impairment. Half-life prolonged and renal clearance decreased in patients with decreased renal function.

Evaluate renal function prior to initiation of therapy and at least annually thereafter.

Monitor more frequently if development of impaired renal function is anticipated (e.g., geriatric patients, those with blood glucose concentrations >300 mg/dL, those who may develop renal dysfunction as a result of polyuria and volume depletion).

Discontinue metformin if patient's eGFR drops below 30 mL/minute per 1.73 m² while on metformin therapy; contraindicated in such patients.

Common Adverse Effects

Immediate-release metformin hydrochloride tablets (>5%): diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache.

Immediate-release metformin hydrochloride oral solution: diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache.

Extended-release metformin hydrochloride tablets (>5%): diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache.

Extended-release metformin hydrochloride tablets (Glumetza) (>5%): hypoglycemia, diarrhea, and nausea.

Drug Interactions

Drugs Affecting or Affected by Transport Systems

Concomitant use of medications (e.g., ranolazine, vandetanib, dolutegravir, cimetidine) that interfere with common renal tubular transport systems involved in renal elimination of metformin hydrochloride (e.g., organic cationic transporter [OCT] 2/multidrug and toxic extrusion [MATE] inhibitors) could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Consider benefits and risk of concomitant use of such medications with metformin.

Drugs That May Antagonize Hypoglycemic Effects

Calcium-channel blocking agents, corticosteroids, thiazide diuretics, estrogens and progestins (e.g., oral contraceptives), isoniazid, niacin, phenothiazines, phenytoin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), thyroid preparations; observe patient closely for evidence of altered glycemic control when such medications are added to or withdrawn from therapy.

Specific Drugs or Foods

metFORMIN Pharmacokinetics

Absorption

Bioavailability

Approximately 50–60% (absolute) with dosages of 0.5–1.5 g.

Onset

Therapeutic response usually apparent within a few days to 1 week. Maximal glycemic response within 2 weeks.

Duration

Blood glucose concentrations increase within 2 weeks following discontinuance of metformin therapy.

Food

Food decreases and slightly delays absorption of immediate-release tablets.

Food increases the extent of absorption and delays the time to peak plasma concentrations of the immediate-release oral solution. Fat content of meals does not appreciably affect the pharmacokinetics of metformin hydrochloride immediate-release oral solution.

Food increases the extent of absorption of extended-release tablets. Peak plasma concentrations and time to achieve peak plasma concentrations not altered by administration of one extended-release preparation with food.

Distribution

Extent

Rapidly distributed into peripheral body tissues and fluids, particularly GI tract.

Slowly distributed into erythrocytes and a deep tissue compartment (probably GI tissue).

Distributed into human breast milk.

Plasma Protein Binding

Negligible.

Elimination

Metabolism

Not metabolized in the liver or GI tract and not excreted into bile. No metabolites identified in humans.

Elimination Route

Excreted in urine (approximately 35–52%) and feces (20–33%). Eliminated as unchanged drug.

Half-life

Approximately 6.2 hours.

Special Populations

Renal impairment may reduce clearance, including in geriatric patients with age-related decline in renal function. Renal impairment results in increased peak plasma concentrations, prolonged time to peak plasma concentration and half-life, and decreased volume of distribution.

Stability

Storage

Oral

Tablets

Immediate-release tablets: Tight, light-resistant containers at 20–25°C (may be exposed to 15–30°C).

Extended-release tablets: Tight, light resistant containers at 20–25°C (may be exposed to 15–30°C).

Metformin/glyburide fixed combination: Light-resistant containers up to 25°C.

Metformin/glipizide fixed combination: 20–25° C (may be exposed to 15–30°C).

Metformin/pioglitazone fixed combination: Tight containers at 25°C.

Metformin/alogliptin fixed combination: Tight containers at 25°C (may be exposed to 15—30°C).

Metformin/linagliptin fixed combination: 20—25°C (may be exposed to 15–30°C); protect from exposure to high humidity.

Metformin/saxagliptin fixed combination: 20–25°C (may be exposed to 15–30°C).

Metformin/sitagliptin fixed combination: 20–25°C (may be exposed to 15–30°C).

Metformin/canagliflozin fixed combination: 20–25°C (may be exposed to 15–30°C). Store and dispense in original container. May store in pillbox for ≤30 days.

Metformin/dapagliflozin: 20–25°C (may be exposed to 15–30°C).

Metformin/empagliflozin: 25°C (may be exposed to 15–30°C).

Metformin/ertugliflozin: 20–25°C (may be exposed to 15–30°C); protect from moisture and store in a dry place.

Solution

15–30°C.

Actions

• Lowers blood glucose concentrations in patients with type 2 diabetes mellitus without increasing insulin secretion from pancreatic β cells. Ineffective in the absence of some endogenous or exogenous insulin.

• Usually does not lower glucose concentrations below euglycemia, but hypoglycemia occasionally may occur with overdosage.

• Lowers both basal (fasting) and postprandial glucose concentrations in patients with type 2 diabetes mellitus. Improves insulin sensitivity by decreasing hepatic glucose production and enhancing insulin-stimulated uptake and utilization of glucose by peripheral tissues (e.g., skeletal muscle, adipocytes). Insulin secretion usually remains unchanged.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Patient Information).

• When metformin hydrochloride is used in fixed combination with other medications, inform patients of other precautionary information about the concomitant agent(s).

• Advise patients to take with meals and to swallow the tablet whole and do not crush, cut, or chew the tablet.

• Advise patients taking extended-release tablet preparations of metformin hydrochloride that occasionally the biologically inert components of the tablet may remain intact and be passed in the stool as a soft, hydrated mass.

• Advise patients or caregivers to use the supplied dosing cup to measure the prescribed amount of metformin hydrochloride oral solution. Inform patients that additional dosing cups or oral dosing syringes may be obtained from their pharmacy.

• Advise patients that if a dose is missed, they should take the next dose at the prescribed time and not to take an extra dose the next day.

• Advise patients to inform their clinician that they are taking metformin hydrochloride prior to any surgical or radiological procedure, as temporary discontinuation may be required.

• Advise patients to inform their clinician of times of stress, such as fever, trauma, or infection, as the dosage of metformin hydrochloride may require adjustment.

• Inform patients of the risks of lactic acidosis, its symptoms, and conditions that predispose to its development. Advise patients to discontinue metformin hydrochloride immediately and to promptly notify their clinician if unexplained hyperventilation, myalgias, malaise, unusual somnolence or other nonspecific symptoms occur.

• Inform patients of the need for regular testing of renal function and hematological parameters.

• Inform patients that hypoglycemia may occur. Inform patients receiving concomitant therapy of the risk of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development.

• Advise patients to avoid excessive alcohol intake.

• Inform patients of the importance of adherence to dietary instructions, regular physical activity, period blood glucose monitoring and glycosylated hemoglobin (hemoglobin A_1c; HbA_1c) testing, and assessment of diabetes mellitus complications.

• Advise females of reproductive potential that treatment with metformin hydrochloride may result in ovulation in some premenopausal anovulatory women, which may lead to unintended pregnancy.

• Advise patient to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

• How long does metformin take to work?
• How do Ozempic and Metformin compare for diabetes?
• When is the best time to take metformin?
• What is the safest diabetes medication?
• Why does metformin cause diarrhea?
• Can you take metformin without food?
• Does metformin lower A1C, if so how much?
• Does metformin cause weight loss?
• What lactic acidosis symptoms are caused by metformin?

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