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metFORMIN (Monograph)

Brand names: Fortamet, Glumetza, Riomet
Drug class: Biguanides
ATC class: A10BA02
VA class: HS502
Chemical name: 1,1-Dimethylbiguanide monohydrochloride
Molecular formula: C4H11N5 • HCl
CAS number: 1115-70-4

Medically reviewed by Drugs.com on Jun 12, 2023. Written by ASHP.

Warning

    Lactic Acidosis

  • Lactic acidosis rare but potentially fatal.1 6 18 20 27 29 30 62 89 96 158 234 254 Increased risk of lactic acidosis in patients with renal impairment and advanced age.1 2 62 96 119 234 254 260 314 352 355 361

  • Generally has occurred in diabetic patients with severe renal insufficiency and concomitant medical and/or surgical problems who were receiving multiple drugs; metformin plasma concentrations >5 mcg/mL often found in patients with lactic acidosis.1 2 3 20 50 62 64 76 96 123 158 164 165 234 254 314

  • Periodically monitor renal function and use the minimum effective dosage.1 32 62 63 65 76 85 91 93 96 119 123 124 158 164 165 234 254 258 287 314 Withhold metformin promptly in patients with any condition associated with hypoxemia, sepsis, or dehydration.1 2 62 63 93 234 260 314 340 Avoid use in patients with clinical or laboratory evidence of hepatic impairment.1 2 63 65 85 91 93 156 158 234 254 314 352 355 Manufacturers state to temporarily discontinue metformin therapy before or at the time of an intravascular (e.g., IV, intra-arterial) iodinated contrast imaging procedure in patients with eGFR of 30–60 mL/minute per 1.73 m2 and in patients with a history of liver disease, alcoholism, or heart failure.1 234 254 330 336 352 355 610 Withhold metformin temporarily in patients undergoing surgery. 1 2 30 62 63 93 158 234 254 261 314 330 336 352 355 610 Concomitant drugs that may affect renal function, produce substantial hemodynamic changes, or alter metformin elimination should be used with caution.1 134 234 254

    However, the American College of Radiology states that in patients with no evidence of acute kidney injury and eGFR ≥30 mL/minute per 1.73 m2, no need to discontinue metformin either before or following the administration of iodinated contrast media, nor is there a need to reassess the patient's renal function after the test or procedure.335

  • Advise patients not to consume excessive amounts of alcohol, acutely or chronically.1 2 63 76 91 93 158 234 314 352 355

  • If lactic acidosis occurs, discontinue metformin and institute general supportive therapy immediately.1 30 260 314 Treat as medical emergency, with immediate hospitalization and treatment required; prompt hemodialysis recommended.1 23 32 62 117 119 234 254 260 314 352 355

Introduction

Antidiabetic agent; a biguanide, chemically and pharmacologically unrelated to sulfonylurea antidiabetic agents.1 2 3 4 18 20 22 23 27 28 29 30 33 72 146 234 254

Uses for metFORMIN

Type 2 Diabetes Mellitus

Used as an adjunct to diet and exercise for the management of type 2 diabetes mellitus.1 3 4 6 8 15 16 17 18 19 20 27 29 95 166 234 254 698 704

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 drugs.1 3 6 15 18 20 22 27 29 30 48 59 78 88 95 97 99 112 134 166 191 234 237 238 239 241 242 248 249 250 254 260 352 355 362 368 370 372 374 376 378 610 698 704

May be used with insulin to improve glycemic control and/or decrease the required dosage of insulin.1 3 6 88 90 94 95 146 698 704

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.234 254 May add a thiazolidinedione antidiabetic agent if patient has inadequate glycemic control with fixed-combination metformin/glyburide therapy.234

Commercially available in fixed combination with pioglitazone for use as an adjunct to diet and exercise in 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.260

Commercially available in fixed combination with the DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, or sitagliptin for use as an adjunct to diet and exercise when treatment with both drug components is appropriate.314 352 368 376 378 610

Commercially available in fixed combinations with the SGLT2 inhibitors canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin for use when treatment with both drug components is appropriate.355 362 370 372 374

Current guidelines for the treatment of type 2 diabetes mellitus generally recommend metformin as first-line therapy in addition to lifestyle modifications in patients with recent-onset type 2 diabetes mellitus or mild hyperglycemia because of its well-established safety and efficacy (i.e., beneficial effects on glycosylated hemoglobin [hemoglobin A1c; HbA1c], weight, and cardiovascular mortality).264 698 704 705 Potential advantages of metformin compared with sulfonylureas or insulin include minimal risk of hypoglycemia, more favorable effects on serum lipids, reduction of hyperinsulinemia, and weight loss or lack of weight gain.1 2 3 6 16 17 18 19 20 27 30 42 60 68 102 134 146 166 264 698 704

In patients with metformin contraindications or intolerance (e.g., risk of lactic acidosis, GI intolerance) or in selected other patients, some experts suggest that initial therapy with a drug from another class of antidiabetic agents (e.g., a GLP-1 receptor agonist, SGLT2 inhibitor, DPP-4 inhibitor, sulfonylurea, thiazolidinedione, basal insulin) may be acceptable based on patient factors.698 704

May need to initiate therapy with 2 agents (e.g., metformin plus another drug) in patients with high initial HbA1c (>7.5% or ≥1.5% above target).698 704 In such patients with metformin intolerance, some experts suggest initiation of therapy with 2 drugs from other antidiabetic drug classes with complementary mechanisms of action.698 704

Consider early initiation of combination therapy for the treatment of type 2 diabetes mellitus to extend the time to treatment failure and more rapidly attain glycemic goals.704

For patients with inadequate glycemic control on metformin monotherapy, consider patient comorbidities (e.g., atherosclerotic cardiovascular disease [ASCVD], established kidney disease, heart failure), hypoglycemia risk, impact on weight, cost, risk of adverse effects, and patient preferences when selecting additional antidiabetic agents for combination therapy.698 699 704 705 706

Consider early introduction of insulin for severe hyperglycemia (e.g., blood glucose ≥300 mg/dL or HbA1c >9–10%), especially if accompanied by catabolic manifestations (e.g., weight loss, hypertriglyceridemia, ketosis) or symptoms of hyperglycemia.698 704

Experts recommend that patients with type 2 diabetes mellitus who have established (or are at a high risk for) ASCVD, established kidney disease, or heart failure receive a GLP-1 receptor agonist or SGLT2 inhibitor with demonstrated cardiovascular disease benefit.704 705 In patients with these comorbidities, consider GLP-1 receptor agonist or SGLT2 inhibitor therapy independently of patient's HbA1c.704

In patients with type 2 diabetes mellitus and CKD, consider a GLP-1 receptor agonist or SGLT2 inhibitor shown to reduce the risk of CKD progression, cardiovascular events, or both, in addition to metformin therapy or in those in whom metformin cannot be used.704 705 706

In patients on metformin monotherapy without established ASCVD or indicators of high ASCVD risk, heart failure, or CKD, base decision regarding addition of other antidiabetic agents on avoidance of adverse effects, cost, and individual patient factors.704

Not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.1

Polycystic Ovary Syndrome

Has been used in the management of metabolic and reproductive abnormalities associated with polycystic ovary syndrome† [off-label].289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312

metFORMIN Dosage and Administration

General

Administration

Oral Administration

Administer orally with meals to reduce adverse GI effects.1 2 3 18 53 85

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.1

Administer extended-release tablets once daily with the evening meal; swallow whole and do not chew, cut, or crush.1 258 260 261 In addition, administer Fortamet extended-release tablets with a full glass of water.258

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.234 254 260 314 355 362 370 372 376 610

Administer extended-release metformin hydrochloride in fixed combination with canagliflozin, dapagliflozin, or empagliflozin once daily with the morning meal.362 370 374

Administer the fixed combination of extended-release metformin hydrochloride and linagliptin once daily with a meal.378 Administer the fixed combination of extended-release metformin hydrochloride and sitagliptin once daily with a meal, preferably the evening meal.352 Administer extended-release metformin hydrochloride in fixed combination with saxagliptin once daily with the evening meal.368

Dosage

Available as metformin hydrochloride; dosage expressed in terms of the salt.1

Individualize dosage carefully based on patient’s glycemic response and tolerance.1 4

Pediatric Patients

Type 2 Diabetes Mellitus
Oral

Immediate-release tablets or immediate-release oral solution in children or adolescents 10–16 years of age: Initially, 500 mg twice daily with meals.1 257

Increase daily dosage in increments of 500 mg at weekly intervals to a maximum of 2 g daily given in 2 divided doses.1 257

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.1 257 Initial dosage of 500 mg once daily has been suggested by some experts.264

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.1 257 May increase dosage from 500 mg twice daily to 850 mg twice daily after 2 weeks.1 257

Clinically important responses generally not observed at dosages <1.5 g daily.1 257

Certain extended-release tablets: Initially, 500 mg once daily with the evening meal.1 Increase daily dosage by 500 mg at weekly intervals based on glycemic control and tolerability up to a maximum of 2 g daily.1 If glycemic control is not achieved with 2 g once daily, consider administering 1 g twice daily.1 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).1 May switch from immediate-release to extended-release metformin hydrochloride tablets at the same total daily dosage, up to 2 g once daily.1 261

Extended-release tablets (Glumetza) in patients ≥18 years of age: Initially, 1 g once daily with the evening meal.261 Increase daily dosage by 500 mg at weekly intervals to a maximum of 2 g once daily with the evening meal.261 If glycemic control not achieved with 2 g once daily, consider administering 1 g twice daily.261

Manufacturer states that based on a clinical trial, therapy with immediate-release metformin may be switched to extended-release metformin (Glumetza) once daily at the same total daily dosage, up to 2 g once daily.261 Following a switch from immediate-release metformin to extended-release metformin hydrochloride (Glumetza), closely monitor glycemic control and adjust dosage accordingly.261

Extended-release tablets (Fortamet) in patients ≥17 years of age: Initially, 1 g once daily with the evening meal; 500 mg once daily may be used when clinically appropriate.258 Increase daily dosage by 500 mg at weekly intervals to a maximum of 2.5 g once daily with the evening meal.258

Manufacturer states that based on a clinical trial, therapy with immediate-release metformin may be switched to extended-release metformin (Fortamet) once daily at the same total daily dosage, up to 2.5 g once daily.258 Following a switch from immediate-release metformin to extended-release metformin hydrochloride (Fortamet), closely monitor glycemic control and adjust dosage accordingly.258

Combined Metformin Hydrochloride and Oral Sulfonylurea Therapy
Oral

Certain extended-release metformin hydrochloride tablets (Fortamet, Glumetza): Manufacturers suggest gradual addition of an oral sulfonylurea antidiabetic agent in patients not responding to 4 weeks of monotherapy with maximum dosages of metformin hydrochloride; continue metformin hydrochloride at the maximum dosage even if prior primary or secondary failure to a sulfonylurea has occurred.258 261 Adjust dosage of metformin hydrochloride (e.g., Fortamet, Glumetza) and the sulfonylurea to obtain the desired level of glycemic control with the minimum effective dosage.258 261 Concomitant metformin and sulfonylurea therapy may increase risk of hypoglycemia; take appropriate precautions.258 261 If patient has not responded satisfactorily to 1–3 months of concomitant therapy with maximum dosages of metformin hydrochloride (e.g., Fortamet, Glumetza) and an oral sulfonylurea, consider therapeutic alternatives, including switching to insulin with or without metformin.258 261

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.254 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.254 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.254 256

Efficacy of metformin hydrochloride and glipizide in fixed combination not established in patients with fasting plasma glucose concentrations >320 mg/dL.254 No experience with total daily dosages exceeding 2 g of metformin hydrochloride and 10 mg of glipizide as initial therapy.254 256

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.254 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).254 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.254

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).254 Use clinical judgment regarding whether to switch to the nearest equivalent dosage or to titrate dosage.254 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.254

Immediate-release Metformin Hydrochloride in Fixed Combination with Glyburide
Oral

Patients not already receiving either glyburide (or another sulfonylurea) or metformin hydrochloride: Initially, 250 mg of metformin hydrochloride and 1.25 mg of glyburide once or twice daily with meals.234 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.234

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.234 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.234

Patients with inadequate glycemic control on the combination of a sulfonylurea and metformin: Initial dosage of the fixed combination should not exceed the patient's current daily dosage of glyburide (or equivalent dosage of another sulfonylurea antidiabetic agent) and metformin hydrochloride.234 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.234

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.260

Patients in whom combination therapy with metformin and pioglitazone considered appropriate: Initially, 500 mg of metformin hydrochloride and 15 mg of pioglitazone twice daily or 850 mg of metformin hydrochloride and 15 mg of pioglitazone once daily.260

Patients inadequately controlled on metformin monotherapy: Initially, 500 mg of metformin hydrochloride and 15 mg of pioglitazone twice daily or 850 mg of metformin hydrochloride and 15 mg of pioglitazone once or twice daily (depending on metformin hydrochloride dosage already being taken).260

Patients inadequately controlled on pioglitazone monotherapy: Initially, 500 mg of metformin hydrochloride and 15 mg of pioglitazone twice daily or 850 mg of metformin hydrochloride and 15 mg of pioglitazone once daily.260

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.260

Patients with NYHA class I or II congestive heart failure: Initially, 500 mg of metformin hydrochloride and 15 mg of pioglitazone or 850 mg of metformin hydrochloride and 15 mg of pioglitazone once daily.260 Initiation of the fixed combination in patients with NYHA class III or IV congestive heart failure contraindicated.260

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.260 Metformin hydrochloride dosages >2 g daily may be better tolerated if given in 3 divided doses daily.260

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

Individualize dosage based on current antidiabetic regimen, effectiveness, and patient tolerability.610 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.610

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

Individualize dosage based on effectiveness and patient tolerability.376 May increase dosage up to a maximum daily dosage of 2 g of metformin hydrochloride and 5 mg of linagliptin.376

Patients not currently receiving metformin hydrochloride: Initially, 1 g of metformin hydrochloride and 5 mg of linagliptin administered in 2 divided doses.376

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.376

Patients currently receiving linagliptin and metformin hydrochloride: Initially, same total daily dosage of each component administered in 2 divided doses daily.376

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

Individualize dosage based on effectiveness and patient tolerability.378 May increase dosage up to a maximum daily dosage of 2 g of metformin hydrochloride and 5 mg of linagliptin.378

Patients not currently receiving metformin hydrochloride: Initially, 1 g of metformin hydrochloride and 5 mg of linagliptin once daily.378

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.378

Patients currently receiving linagliptin and metformin hydrochloride: Initially, a total daily metformin hydrochloride dosage similar to the patient’s existing dosage and 5 mg of linagliptin, administered once daily.378

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

Patients inadequately controlled on monotherapy with saxagliptin 5 mg daily: Initially, 500 mg of metformin hydrochloride and 5 mg of saxagliptin once daily; increase dosage gradually to minimize adverse GI effects of metformin.368

Patients inadequately controlled on monotherapy with extended-release metformin hydrochloride: Dosage of the fixed combination should provide metformin hydrochloride at the current dosage or the nearest therapeutically appropriate dosage.368

Following a switch from immediate-release to extended-release metformin hydrochloride, closely monitor glycemic control and adjust dosage accordingly.368

Patients inadequately controlled on monotherapy with saxagliptin 2.5 mg daily: Initially, 1 g of metformin hydrochloride and 2.5 mg of saxagliptin daily.368 Use the individual components in patients who require 2.5 mg of saxagliptin and are either metformin naive or require a metformin hydrochloride dose >1 g.368

If used with a potent CYP3A4/5 inhibitor, limit dosage of saxagliptin to 2.5 mg once daily.368

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.314

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.314

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.314

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).352

Efficacy and safety of switching therapy from oral antidiabetic agents other than sitagliptin or metformin hydrochloride to the fixed combination of sitagliptin and metformin hydrochloride not established.314

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.352

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.352

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.314 352

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).352

Efficacy and safety of switching therapy from oral antidiabetic agents other than sitagliptin or metformin hydrochloride to the fixed combination of sitagliptin and metformin hydrochloride not established.352

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

Individualize dosage based on patient's current antidiabetic regimen.370 May increase dosage gradually based on effectiveness and tolerability.370

Patients not currently receiving either canagliflozin or metformin hydrochloride: Initially, 500 mg of metformin hydrochloride and 50 mg of canagliflozin twice daily.370

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.370 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.370

Patients currently receiving canagliflozin: Initially, 1 g of metformin hydrochloride and same daily dosage of canagliflozin administered in 2 divided doses.370

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.370

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

Individualize dosage based on patient's current antidiabetic regimen.370 May increase dosage gradually based on effectiveness and tolerability.370

Patients not currently receiving either canagliflozin or metformin hydrochloride: Initially, 1 g of metformin hydrochloride and 100 mg of canagliflozin once daily.370

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.370 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.370

Patients currently receiving canagliflozin: Initially, 1 g of metformin hydrochloride and same daily dosage of canagliflozin administered once daily.370

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.370

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.362 May increase dosage gradually based on effectiveness and tolerability.362

Patients not currently receiving dapagliflozin: Initially, 5 mg of the dapagliflozin component once daily.362 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.362

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.362

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

Individualize dosage based on the patient's current antidiabetic regimen.372 May increase dosage gradually based on effectiveness and tolerability.372

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.372

Patients currently receiving empagliflozin: Initially, 1 g of metformin hydrochloride and same daily dosage of empagliflozin administered in 2 divided doses.372

Patients currently receiving empagliflozin and metformin hydrochloride: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and same daily dosage of empagliflozin, administered in 2 divided doses.372

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

Individualize dosage based on the patient's current antidiabetic regimen.374 May increase dosage gradually based on effectiveness and tolerability.374

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.374

Patients currently receiving empagliflozin: Initially, 1 g of metformin hydrochloride and same daily dosage of empagliflozin administered once daily.374

Patients currently receiving empagliflozin and metformin hydrochloride: Initially, a total daily metformin hydrochloride dosage similar to patient's existing dosage and same daily dosage of empagliflozin, administered once daily.374

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.355 May increase dosage gradually based on effectiveness and tolerability.355

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.355

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 a total daily ertugliflozin dosage similar to the patient's existing dosage, given in 2 divided doses daily.355

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.355

Metformin Hydrochloride Dosage in Patients Receiving Insulin
Oral

Certain extended-release tablets (Fortamet, Glumetza): Initially, 500 mg once daily; concurrent insulin dosage initially remains unchanged.258 261 Increase metformin hydrochloride dosage by 500 mg daily at weekly intervals until adequate glycemic control is achieved or a maximum daily dosage of 2.5 g (Fortamet)258 or 2 g (Glumetza)261 is reached. When fasting plasma glucose concentration decreases to <120 mg/dL, decrease insulin dosage by 10–25%.258 261 Individualize further dosage adjustments according to glycemic response.258 261

Polycystic Ovary Syndrome† [off-label]
Oral

In general, 1.5–2.25 g daily in divided doses.291 292 294 296 299 300 301 302 303 305 306 307

Prescribing Limits

Pediatric Patients

Type 2 Diabetes Mellitus
Oral

Children 10–16 years of age: Maximum 2 g daily as immediate-release tablets or immediate-release oral solution.1 257

Adults

Type 2 Diabetes Mellitus
Metformin Hydrochloride Monotherapy
Oral

Maximum 2.55 g daily as immediate-release tablets or immediate-release oral solution, 2.5 g daily as Fortamet extended-release tablets, or 2 g daily as certain other extended-release tablets.1 2 3 4 18 22 85 257 258 Switch to immediate-release tablets for further dosage titration if required dosage exceeds 2 g daily.1

Metformin Hydrochloride in Fixed Combination with Glyburide
Oral

Maximum daily dosage is 2 g of metformin hydrochloride and 20 mg of glyburide.234

Metformin Hydrochloride in Fixed Combination with Glipizide
Oral

Maximum daily dosage is 2 g of metformin hydrochloride and 20 mg of glipizide.254 256

Metformin Hydrochloride in Fixed Combination with Linagliptin (Jentadueto, Jentadueto XR)
Oral

Maximum daily dosage is 2 g of metformin hydrochloride and 5 mg of linagliptin.376 378

Metformin Hydrochloride in Fixed Combination with Saxagliptin (Kombiglyze XR)
Oral

Maximum daily dosage is 2 g of metformin hydrochloride and 5 mg of saxagliptin.368

Metformin Hydrochloride in Fixed Combination with Sitagliptin (Janumet, Janumet XR)
Oral

Maximum daily dosage is 2 g of metformin hydrochloride and 100 mg of sitagliptin.314 352

Metformin Hydrochloride in Fixed Combination with Canagliflozin (Invokamet, Invokamet XR)
Oral

Patients with eGFR ≥60 mL/minute per 1.73 m2: Maximum daily dosage is 2 g of metformin hydrochloride and 300 mg of canagliflozin.370

Patients with eGFR 45 to <60 mL/minute per 1.73 m2: Maximum daily dosage is 2 g of metformin hydrochloride and 100 mg of canagliflozin.370

Metformin Hydrochloride in Fixed Combination with Dapagliflozin (Xigduo XR)
Oral

Maximum daily dosage is 2 g of metformin hydrochloride and 10 mg of dapagliflozin.362

Metformin Hydrochloride in Fixed Combination with Empagliflozin (Synjardy, Synjardy XR)
Oral

Maximum daily dosage is 2 g of metformin hydrochloride and 25 mg of empagliflozin.372 374

Metformin Hydrochloride in Fixed Combination with Ertugliflozin (Segluromet)
Oral

Maximum daily dosage is 2 g of metformin hydrochloride and 15 mg of ertugliflozin.355

Special Populations

Renal Impairment

eGFR 30–45 mL/minute per 1.73 m2: Initiation of metformin 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.1 330 336

eGFR <30 mL/minute per 1.73 m2: Contraindicated; discontinue in patients already receiving metformin.1 165 260 287 314 330 336

Hepatic Impairment

Avoid use in those with clinical or laboratory evidence of hepatic disease.1 165 260 287 314 330 336

Geriatric Patients

In general, do not titrate to the maximum dosage recommended for younger adults;2 3 4 165 254 258 261 314 limited data suggest reducing initial dosage by approximately 33% in geriatric patients.30 174

Monitor renal function regularly to determine appropriate dosage.1 2 3 4 164 165 260 314

Detailed Metformin dosage information

Cautions for metFORMIN

Contraindications

Warnings/Precautions

Warnings

Lactic Acidosis

See Boxed Warning.

Other Warnings and Precautions

Hypoglycemia

Uncommon in patients receiving metformin as monotherapy.1 15 30 78 94 99 Debilitated, malnourished, or geriatric patients and patients with renal or hepatic impairment or adrenal or pituitary insufficiency may be particularly susceptible.1 2 Strenuous exercise, alcohol ingestion, insufficient caloric intake, or use in combination with other antidiabetic agents may increase risk.1 2 Hypoglycemia may be difficult to recognize in geriatric patients or in those receiving β-adrenergic blocking agents.1 83 91 128 143 153 159 (See Specific Drugs or Foods under Interactions.)

Hematologic Effects

Decreased serum vitamin B12 concentrations, 1 18 with or without clinical manifestations (e.g., anemia).1

Symptoms rapidly reversible following discontinuation of metformin or supplementation with vitamin B12.1 3 6 20 30 70 77 82 134 Monitor hematologic parameters (e.g., hemoglobin, serum vitamin B12 concentrations)1 82 114 122 134 148 698 prior to initiation of therapy and at least annually during treatment and any abnormality properly investigated.1

In patients who develop neuropathy while on metformin, monitor vitamin B12 levels698 704 and administer supplementation if needed;698 consider periodic supplementation with parenteral vitamin B12 in patients at high risk for developing subnormal serum vitamin B12 concentrations (e.g., alcoholics, patients with low calcium or vitamin B12 intake or absorption).1 82 114 122 134 148

Macrovascular Outcomes

The manufacturer states that there have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with metformin.1

Concurrent Illness

Evaluate serum electrolytes and ketones, blood glucose, and if indicated, blood pH, lactate, pyruvate, and metformin concentrations for evidence of ketoacidosis or lactic acidosis.1 88 134 156 169

Temporary withdrawal of metformin therapy and administration of insulin may be required to maintain glycemic control during periods of stress.1

Use of Fixed Combinations

When used in fixed combination with other drugs, consider the cautions, precautions, contraindications, and interactions associated with the concomitant agent(s).234 237 254 260 314 352 355 362 368 370 372 374 376 378 610

Specific Populations

Pregnancy

Category B.1

Available studies suggest no clear association between metformin use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes.1 Use metformin during pregnancy only when clearly needed.3 4

Most clinicians recommend use of insulin during pregnancy in diabetic patients to maintain optimum control of blood glucose concentrations.1 3 4 18 72 88 92

Lactation

Distributed into milk in rats; small amounts distributed into human milk.1 260 284 285 286 Consider developmental and health benefits of breastfeeding along with mother's clinical need for the drug and potential adverse effects on breastfed child (e.g., hypoglycemia).234 254 Monitor breastfed infants for signs of hypoglycemia (e.g., jitters, cyanosis, apnea, hypothermia, excessive sleepiness, poor feeding, seizures).234 254

Pediatric Use

Safety and efficacy of metformin as immediate-release tablets or immediate-release oral solution in children <10 years of age have not been established.1 257

Safety and efficacy of metformin as extended-release tablets in children <17 years of age have not been established.1 258

Safety and efficacy of metformin in fixed combination with glipizide, pioglitazone, or sitagliptin in children have not been established.1 3 4 30 134 254 260 314 Data from a clinical trial in children 9–16 years of age comparing combined therapy with metformin and glyburide with each drug as monotherapy did not reveal unexpected safety findings.234

Geriatric Use

Insufficient number of geriatric patients in controlled clinical trials of metformin hydrochloride immediate-release (Glucophage) and extended-release tablets (Glucophage XR, Glumetza) to determine if such patients respond differently than younger adults.1 261 314 With another extended-release preparation of metformin hydrochloride (Fortamet), no overall differences in safety or efficacy in geriatric patients were observed compared with younger adults.258

Use with caution, since renal function declines with age.1 3 4 30 85 174 234 254 314

Monitor renal function periodically.1 2 3 4 164 165 314

Do not initiate in patients ≥80 years of age without confirmation of adequate renal function as measured by Clcr.1 209 314

Geriatric patients particularly susceptible to hypoglycemia,1 2 which may be difficult to recognize.1 83 91 128 143 153 159

Renal Impairment

Do not use in patients with severe renal disease or dysfunction.1 165 260 287 314 330 336 (See Contraindications.)

Evaluate renal function prior to initiation of therapy and at least annually thereafter.1 2 77 85 234 254 260 330

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).1 156 234 254 260 330

Discontinue metformin if patient's eGFR <30 mL/minute per 1.73 m2 or drops below 30 mL/minute per 1.73 m2 while on metformin therapy; contraindicated in such patients.1 234 254 257 260 330 336

Hepatic Impairment

Generally avoid use in patients with clinical or laboratory evidence of hepatic disease.1 165 260 287 314 330 336 Elimination of lactate may be substantially reduced.1 (See Boxed Warning.)

Common Adverse Effects

Diarrhea,1 31 48 49 53 78 109 118 122 135 nausea,1 31 53 78 109 118 122 vomiting,1 118 122 abdominal bloating, abdominal cramping or pain,1 31 35 42 53 118 122 flatulence,1 anorexia.1 3 6 18

Drug Interactions

Cationic Agents Secreted by Proximal Renal Tubules

Pharmacokinetic interaction with cimetidine (decreased excretion of metformin).1 75 234 254 260 314

Potential pharmacokinetic interaction with other cationic drugs that undergo substantial tubular secretion (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, vancomycin).1 30 254 260 314

Monitor carefully; consider dosage adjustment of either agent.1 314

Protein-bound Drugs

Pharmacokinetic interaction unlikely.1

Drugs That May Antagonize Hypoglycemic Effects

Calcium-channel blocking agents, corticosteroids, thiazide diuretics, estrogens and progestins (e.g., oral contraceptives), isoniazid, niacin, phenothiazines, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline); observe patient closely for evidence of altered glycemic control when such drugs are added to or withdrawn from therapy.1 30 80 85 91 120 121 134 139 143 151 152 153 154 159 160

Specific Drugs or Foods

Drug

Interaction

Comments

Acarbose

Acute decrease in metformin bioavailability in single-dose study138 201

ACE inhibitors

Potential risk of hypoglycemia/hyperglycemia when ACE inhibitor therapy is initiated/withdrawn131 132 134 152 155 160

Monitor blood glucose concentrations during dosage adjustments with either agent130 131 132 134 152 155 160

Alcohol

Increased risk of hypoglycemia and lactic acidosis1 2 18 33 63 72 76 91 93 107 143

Avoid excessive alcohol intake1 314

Antidiabetic agents (e.g., sulfonylureas, meglitinides, insulin)

Possible hypoglycemia1 15 78 94 99 260

May need to reduce dosage of concomitant antidiabetic agent1

β-Adrenergic blocking agents

May impair glucose tolerance; 73 143 152 153 159 may increase frequency or severity of hypoglycemia and hypoglycemia-induced complications91 127 153 159

If concomitant therapy necessary, a β1-selective adrenergic blocking agent or β-adrenergic blocking agents with intrinsic sympathomimetic activity preferred36 143 152 160 173

Carbonic anhydrase inhibitors

May reduce serum bicarbonate concentrations and induce non-anion gap, hyperchloremic metabolic acidosis; may increase risk for lactic acidosis1 234 254 260

Consider more frequent monitoring of patients receiving such concomitant therapy1 234 254 260

Cimetidine

Possible decreased excretion of metformin1 75 234 254 260 314

Increased peak concentrations and AUC of metformin; negligible effects on cimetidine pharmacokinetics1 75 314

Carefully monitor patient; consider need for dosage adjustment1 314

Clomiphene

Possible resumption of ovulation in premenopausal patients with polycystic ovary syndrome210 211 212 234

Furosemide

Increased peak concentrations of metformin and decreased peak concentrations and terminal half-life of furosemide in single-dose study1 314

Glyburide

Pharmacokinetics and pharmacodynamics of metformin not altered in single-dose study1 260 261 314

Guar gum

Reduced and delayed GI absorption of metformin 18 85 99 106

Nifedipine

Enhanced absorption and increased urinary excretion of metformin; minimal effects on nifedipine pharmacokinetics1 314

Thiazide diuretics

May exacerbate diabetes mellitus1 91 139 143 151 152 153 154 159 160

Consider using less diabetogenic diuretic (e.g., potassium-sparing diuretic), reducing dosage of or discontinuing diuretic, or increasing dosage of oral antidiabetic agent73 134 152 153 154 159 160
Metformin drug interactions (more detail)

metFORMIN Pharmacokinetics

Absorption

Bioavailability

Approximately 50–60% (absolute) with dosages of 0.5–1.5 g.1 2 3 4 18 33 43 50 65 72 85 89

Onset

Therapeutic response usually apparent within a few days to 1 week.18 53 72 98 134 Maximal glycemic response within 2 weeks.18 53 72 98 134

Duration

Blood glucose concentrations increase within 2 weeks following discontinuance of metformin therapy.53 134

Food

Food decreases and slightly delays absorption of immediate-release tablets.1 2 3 4 18 208 314

Food increases the extent of absorption of extended-release tablets (Glucophage XR, Fortamet).1 258 Peak plasma concentrations and time to achieve peak plasma concentrations not altered by administration of one extended-release preparation (Glucophage XR) with food; 1 food increases peak plasma concentrations and prolongs time to peak plasma concentrations of another extended-release tablet preparation (Fortamet).258

Food increases the extent of absorption and delays the time to peak plasma concentrations of the immediate-release oral solution.257 Fat content of meals does not appreciably affect the pharmacokinetics of metformin hydrochloride immediate-release oral solution.257

Distribution

Extent

Rapidly distributed into peripheral body tissues and fluids, particularly GI tract.30 50 65 72 89 134 162 167

Slowly distributed into erythrocytes and a deep tissue compartment (probably GI tissue).30 50 65 72 89 134 162 167

Plasma Protein Binding

Negligible.1 18 50 51 65 85 89

Elimination

Metabolism

Not metabolized in the liver or GI tract and not excreted into bile.1 50 51 89 No metabolites identified in humans.1 50 51 89 314

Elimination Route

Excreted in urine (approximately 35–52%)50 51 89 and feces (20–33%).6 33 43 50 72 89 Eliminated as unchanged drug.1 2 6 33 50 63 65 75 85 89 314

Half-life

Approximately 6.2 hours.1 2 6 18 33 38 50 51 65 85 89 125 134 314

Special Populations

Renal impairment may reduce clearance, including in geriatric patients with age-related decline in renal function.1 33 51 174 Renal impairment results in increased peak plasma concentrations, prolonged time to peak plasma concentration and half-life, and decreased volume of distribution.1 3 51 174

Stability

Storage

Oral

Tablets

Immediate-release tablets: Tight, light-resistant containers at 20–25°C (may be exposed to 15–30°C).1

Extended-release tablets: Tight, light resistant containers at 20–25°C (may be exposed to 15–30°C).1 258

Metformin/glyburide fixed combination: Light-resistant containers at 25°C.234

Metformin/glipizide fixed combination: 20–25° C (may be exposed to 15–30°C).254

Metformin/pioglitazone fixed combination: Tight containers at 25°C.260

Metformin/linagliptin fixed combination: 25°C (may be exposed to 15–30°C); protect from exposure to high humidity.376 378

Metformin/saxagliptin fixed combination: 20–25°C (may be exposed to 15–30°C).368

Metformin/sitagliptin fixed combination: 20–25°C (may be exposed to 15–30°C).314

Metformin/canagliflozin fixed combination: 20–25°C (may be exposed to 15–30°C).370 Store and dispense in original container.370 May store in pillbox for ≤30 days.370

Metformin/dapagliflozin: 20–25°C (may be exposed to 15–30°C).362

Metformin/empagliflozin: 25°C (may be exposed to 15–30°C).372 374

Metformin/ertugliflozin: 20–25°C (may be exposed to 15–30°C); protect from moisture and store in a dry place.355

Solution

15–30°C.257

Actions

Advice to Patients

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

metFORMIN Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

500 mg/5 mL*

metFORMIN Hydrochloride Solution

Riomet

Ranbaxy

Tablets, extended-release

500 mg*

Fortamet

Shionogi Pharma

Glumetza

Depomed

metFORMIN Hydrochloride Extended-Release Tablets

750 mg*

metFORMIN Hydrochloride Extended-Release Tablets

1 g*

Fortamet

Shionogi Pharma

Glumetza

Depomed

metFORMIN Hydrochloride Extended-Release Tablets

Tablets, film-coated

500 mg*

metFORMIN Hydrochloride Tablets

625 mg*

metFORMIN Hydrochloride Tablets

750 mg*

metFORMIN Hydrochloride Tablets

850 mg*

metFORMIN Hydrochloride Tablets

1 g*

metFORMIN Hydrochloride Tablets

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

metFORMIN Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release

500 mg with Immediate-release Canagliflozin (anhydrous) 50 mg

Invokamet XR

Janssen

500 mg with Immediate-release Canagliflozin (anhydrous) 150 mg

Invokamet XR

Janssen

500 mg with Immediate-release Dapagliflozin Propanediol 5 mg (of dapagliflozin)

Xigduo XR

AstraZeneca

500 mg with Immediate-release Dapagliflozin Propanediol 10 mg (of dapagliflozin)

Xigduo XR

AstraZeneca

500 mg with Immediate-release Saxagliptin 5 mg

Kombiglyze XR

AstraZeneca

500 mg with Immediate-release Sitagliptin 50 mg

Janumet XR

Merck

1 g with Immediate-release Canagliflozin (anhydrous) 50 mg

Invokamet XR

Janssen

1 g with Immediate-release Canagliflozin (anhydrous) 150 mg

Invokamet XR

Janssen

1 g with Immediate-release Dapagliflozin Propanediol 2.5 mg (of dapagliflozin)

Xigduo XR

AstraZeneca

1 g with Immediate-release Dapagliflozin Propanediol 5 mg (of dapagliflozin)

Xigduo XR

AstraZeneca

1 g with Immediate-release Dapagliflozin Propanediol 10 mg (of dapagliflozin)

Xigduo XR

AstraZeneca

1 g with Immediate-release Empagliflozin 5 mg

Synjardy XR

Boehringer Ingelheim

1 g with Immediate-release Empagliflozin 10 mg

Synjardy XR

Boehringer Ingelheim

1 g with Immediate-release Empagliflozin 12.5 mg

Synjardy XR

Boehringer Ingelheim

1 g with Immediate-release Empagliflozin 25 mg

Synjardy XR

Boehringer Ingelheim

1 g with Immediate-release Linagliptin 2.5 mg

Jentadueto XR

Boehringer Ingelheim

1 g with Immediate-release Linagliptin 5 mg

Jentadueto XR

Boehringer Ingelheim

1 g with Immediate-release Saxagliptin 2.5 mg

Kombiglyze XR

AstraZeneca

1 g with Immediate-release Saxagliptin 5 mg

Kombiglyze XR

AstraZeneca

1 g with Immediate-release Sitagliptin 50 mg

Janumet XR

Merck

1 g with Immediate-release Sitagliptin 100 mg

Janumet XR

Merck

Tablets, film-coated

250 mg with Glipizide 2.5 mg*

metFORMIN Hydrochloride and Glipizide Tablets

250 mg with Glyburide 1.25 mg*

metFORMIN Hydrochloride and Glyburide Tablets

500 mg with Alogliptin Benzoate 12.5 mg (of alogliptin)

Kazano

Takeda

500 mg with Canagliflozin (anhydrous) 50 mg

Invokamet

Janssen

500 mg with Canagliflozin (anhydrous) 150 mg

Invokamet

Janssen

500 mg with Empagliflozin 5 mg

Synjardy

Boehringer Ingelheim

500 mg with Empagliflozin 12.5 mg

Synjardy

Boehringer Ingelheim

500 mg with Ertugliflozin L-pyroglutamic Acid 2.5 mg (of ertugliflozin)

Segluromet

Merck

500 mg with Ertugliflozin L-pyroglutamic Acid 7.5 mg (of ertugliflozin)

Segluromet

Merck

500 mg with Glipizide 2.5 mg*

metFORMIN Hydrochloride and Glipizide Tablets

500 mg with Glipizide 5 mg*

metFORMIN Hydrochloride and Glipizide Tablets

500 mg with Glyburide 2.5 mg*

metFORMIN Hydrochloride and Glyburide Tablets

500 mg with Glyburide 5 mg*

MetFORMIN Hydrochloride and Glyburide Tablets

500 mg with Linagliptin 2.5 mg

Jentadueto

Boehringer Ingelheim

500 mg with Pioglitazone Hydrochloride 15 mg (of pioglitazone)

Actoplus Met

Takeda

500 mg with Sitagliptin Phosphate 50 mg (of sitagliptin)

Janumet

Merck

850 mg with Linagliptin 2.5 mg

Jentadueto

Boehringer Ingelheim

850 mg with Pioglitazone Hydrochloride 15 mg (of pioglitazone)

Actoplus Met

Takeda

1 g with Alogliptin Benzoate 12.5 mg (of alogliptin)

Kazano

Takeda

1 g with Canagliflozin (anhydrous) 50 mg

Invokamet

Janssen

1 g with Canagliflozin (anhydrous) 150 mg

Invokamet

Janssen

1 g with Empagliflozin 5 mg

Synjardy

Boehringer Ingelheim

1 g with Empagliflozin 12.5 mg

Synjardy

Boehringer Ingelheim

1 g with Ertugliflozin L-pyroglutamic Acid 2.5 mg (of ertugliflozin)

Segluromet

Merck

1 g with Ertugliflozin L-pyroglutamic Acid 7.5 mg (of ertugliflozin)

Segluromet

Merck

1 g with Linagliptin 2.5 mg

Jentadueto

Boehringer Ingelheim

1 g with Sitagliptin Phosphate 50 mg (of sitagliptin)

Janumet

Merck

AHFS DI Essentials™. © Copyright 2024, Selected Revisions June 21, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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6. Bailey CJ. Biguanides and NIDDM. Diabetes Care. 1992; 15:755-72. http://www.ncbi.nlm.nih.gov/pubmed/1600835?dopt=AbstractPlus

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22. Reaven GM, Johnston P, Hollenbeck CB et al. Combined metformin-sulfonylurea treatment of patients with noninsulin-dependent diabetes in fair to poor glycemic control. J Clin Endocrinol Metab. 1992; 74:1020-6. http://www.ncbi.nlm.nih.gov/pubmed/1569149?dopt=AbstractPlus

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26. Kerr CP. Improving outcomes in diabetes: a review of the outpatient care of NIDDM patients. J Fam Pract. 1995; 40:63-75. http://www.ncbi.nlm.nih.gov/pubmed/7807040?dopt=AbstractPlus

27. Gerich JE. Oral hypoglycemic agents. N Engl J Med. 1989; 321:1231-45. http://www.ncbi.nlm.nih.gov/pubmed/2677730?dopt=AbstractPlus

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31. DeFronzo RA, Barzilai N, Simonson DC. Mechanism of metformin action in Obese and Lean Noninsulin-Dependent Diabetic Subjects. J Clin Endocrinol Metab. 1991; 73:1294-1300. http://www.ncbi.nlm.nih.gov/pubmed/1955512?dopt=AbstractPlus

32. Gan SC, Barr J, Arieff AI et al. Biguanide-associated lactic acidosis. Arch Intern Med. 1992; 152:2333-36. http://www.ncbi.nlm.nih.gov/pubmed/1444694?dopt=AbstractPlus

33. Anon. Metformin. Phase III Drug Profiles. 1994; 4:1-15.

34. Nagi DK, Yudkin JS. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. Diabetes Care. 1993; 16:621-629. http://www.ncbi.nlm.nih.gov/pubmed/8462390?dopt=AbstractPlus

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