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Metformin Hydrochloride

Pronunciation: met-FORE-min HYE-droe-KLOR-ide
Class: Biguanide

Trade Names

- Tablets, ER 500 mg
- Tablets, ER 1,000 mg

- Tablets 500 mg
- Tablets 850 mg
- Tablets 1,000 mg

Glucophage XR
- Tablets, ER 500 mg
- Tablets, ER 750 mg

- Tablets, ER 500 mg
- Tablets, ER 1,000 mg

- Solution, oral 500 mg per 5 mL

Apo-Metformin (Canada)
CO Metformin Coated (Canada)
Gen-Metformin (Canada)
Glumetza (Canada)
Novo-Metformin (Canada)
Nu-Metformin (Canada)
PMS-Metformin (Canada)
RAN-Metformin (Canada)
ratio-Metformin (Canada)
Sandoz Metformin FC (Canada)


Decreases blood glucose by decreasing hepatic glucose production. May also decrease intestinal absorption of glucose and increase response to insulin.



Absolute bioavailability is approximately 50% to 60%. T max is 4 to 8 h; C max is approximately 0.6 to 1.8 mcg/mL (ER). Food decreases the extent of absorption and increases T max (immediate-release [IR]).


The apparent Vd is approximately 654 L; protein binding is negligible.


The major route for excretion is renal via tubular secretion as unchanged. The plasma elimination half-life is 6.2 h; the elimination half-life in blood is 17.6 h (5.4 h for Fortamet ).

Special Populations

Renal Function Impairment

In patients with renal insufficiency, the plasma and blood half-life is prolonged and renal Cl is decreased.

Hepatic Function Impairment

No studies have been conducted in patients with hepatic insufficiency.


Limited data in healthy elderly subjects suggest that total plasma Cl is decreased, half-life is prolonged, and C max is increased compared with healthy younger subjects.

Indications and Usage

Adjunct to diet and exercise to lower blood glucose in patients with type 2 diabetes mellitus. Metformin IR tablets and oral solution are indicated in patients 10 yr of age and older. The ER tablets are indicated in patients 17 yr of age and older (18 yr of age and older for Glumetza ). In combination with a sulfonylurea or insulin to improve glycemic control, metformin is indicated in patients 17 yr of age and older (18 yr of age and older for Glumetza ).

Unlabeled Uses

Treatment of anovulation in women with polycystic ovary syndrome; treatment of antipsychotic-induced weight gain.


Renal disease or dysfunction as suggested by serum creatinine of 1.5 mg/dL or higher in men or 1.4 mg/dL or higher in women, or abnormal CrCl; conditions that predispose to renal function impairment (eg, CV collapse, acute MI, septicemia); in patients undergoing radiologic studies involving parenteral administration of iodinated contrast material (potential to acutely alter renal function); acute or chronic metabolic acidosis, including diabetic ketoacidosis; CHF requiring pharmacologic treatment; hypersensitivity to any component of the product.

Dosage and Administration

Dosages of metformin must be individualized on the basis of both effectiveness and tolerance, while not exceeding the max recommended daily dose.

Concomitant Insulin Therapy

PO Initiate metformin IR or ER therapy at 500 mg once daily in patients receiving insulin therapy. The metformin dose may be increased 500 mg after 1 wk and by 500 mg every wk thereafter until adequate glycemic control is achieved (max, 2,500 mg/day of metformin IR and 2,000 mg/day of metformin ER [2,500 mg/day of Fortamet ]). It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose decreases to less than 120 mg/dL in patients receiving metformin IR or ER.

Concomitant Sulfonylurea Therapy

PO If patient has not responded to 4 wk of max metformin monotherapy, consider gradual addition of an oral sulfonylurea while continuing the max metformin dose. Attempts should be made to identify the minimum effective dose of each drug.

Transfer From Other Antidiabetic Therapy

PO When transferring patients from standard oral hypoglycemic agents other than chlorpropamide, no transition period generally is needed. When transferring from chlorpropamide, exercise care during the first 2 wk because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.

Glucophage , Riomet (Metformin IR)

PO Initial dosage: 500 mg twice daily or 850 mg once daily given with meals, increase by 500 mg weekly or 850 mg every 2 wk (max, 2,000 mg/day) in divided doses. Patients can also be titrated from 500 mg twice daily to 850 mg twice daily after 2 wk. For patients requiring additional glycemic control, Glucophage or Riomet may be given up to a max dosage of 2,550 mg/day. Doses more than 2,000 mg may be better tolerated given 3 times daily with meals.

Fortamet (Metformin ER)

PO 1,000 mg once daily with a full glass of water with evening meal, increase by 500 mg weekly (max, 2,500 mg once daily).

Glucophage XR (Metformin ER)

PO Initial dosage: 500 mg once daily with evening meal, increase by 500 mg every wk (max, 2,000 mg once daily). If glycemic control is not achieved on Glucophage XR 2,000 mg once daily, consider a trial of Glucophage XR 1,000 mg twice daily. If higher doses of metformin are required, administer at total daily dose up to 2,550 mg in divided daily doses as previously described.

Glumetza (Metformin ER)

PO Initial dosage: 1,000 mg once daily with food, preferably in the evening. The dose may be increased in increments of 500 mg weekly (max, 2,000 mg once daily with evening meal). If glycemic control is not achieved with 2,000 mg once daily, consider a trial of 1,000 mg twice daily.

Glucophage , Riomet (Metformin IR)
Children 10 yr of age and older IR tablet or oral solution

PO 500 mg twice daily with meals. Dosage may be increased in weekly 500 mg increments to a max of 2,000 mg/day in divided doses.

General Advice

  • Fortamet tablets, Glucophage XR tablets, and Glumetza tablets must be swallowed whole and never broken, crushed, or chewed.


Store tablets and oral solution at controlled room temperature (59° to 86°F).


Protect from moisture and light. Avoid excessive heat and humidity.

Glucophage , Glucophage XR

Protect from light.

Drug Interactions


Potentiates effect of metformin on lactate metabolism.

Cationic drugs (eg, amiloride, digoxin, quinidine)

May increase metformin serum concentration by competing for tubular secretion.


Increases metformin serum concentration.

Drugs tending to produce hyperglycemia (eg, calcium channel blockers, corticosteroids, diuretics, estrogens, isoniazid, nicotinic acid, oral contraceptives, phenothiazines, phenytoin, sympathomimetics, thyroid products)

Closely monitor blood glucose control when starting or stopping these agents.


May increase metformin serum concentration; metformin may reduce furosemide serum concentration.


Glyburide blood levels may be decreased.

Iodinated contrast material

May cause acute renal failure and has been associated with lactic acidosis in patients receiving metformin.


Increases metformin serum concentration.

Laboratory Test Interactions

None well documented.

Adverse Reactions


Palpitation (1% to 5%).


Asthenia (9%); headache (6%); dizziness, light-headedness (1% to 5%).


Increased sweating, nail disorder, rash (1% to 5%).


Rhinitis (6%); taste disorder (1% to 5%).


Diarrhea (53%); nausea/vomiting (26%); flatulence (12%); indigestion (7%); abdominal discomfort (6%); dyspepsia (5%); abdominal pain (3%); abnormal stools, constipation, distended abdomen, heartburn, taste disturbance (1% to 5%).


Hypoglycemia (1% to 5%).


Myalgia (1% to 5%).


Dyspnea, upper respiratory tract infection (1% to 5%).


Infection (21%); accidental injury (7%); chest discomfort, chills, flu syndrome, flushing (1% to 5%).



Lactic acidosis

Can occur as a result of metformin accumulation (eg, renal function impairment) or with pathophysiologic conditions associated with tissue hypoperfusion and hypoxia. When it occurs, it is fatal in approximately 50% of cases. The risk of lactic acidosis increases with the degree of renal function impairment and the patient's age.


Monitor renal function before starting therapy and at least annually thereafter. Regularly monitor renal function in elderly patients, especially patients 80 yr of age and older. Periodically measure fasting blood glucose and glycosylated hemoglobin levels. Monitor hematologic parameters initially and periodically (at least on an annual basis).


Category B . Insulin is recommended to maintain blood glucose levels during pregnancy.


Metformin is excreted, but is considered compatible with breast-feeding.


Fortamet , Glucophage XR (Metformin ER)

Safety and efficacy not established in patients younger than 17 yr of age.

Glumetza ER (Metformin ER)

Safety and efficacy not established in patients younger than 18 yr of age.

Glucophage , Riomet (Metformin IR)

Safety and efficacy not established in children younger than 10 yr of age.


Use with caution. Max doses are generally not used because of age-related decreases in renal function. Do not initiate metformin in patients 80 yr of age and older unless measurement of CrCl demonstrates that renal function is not reduced.

Renal Function

Decreased renal function results in decreased renal Cl and prolongation of the metformin half-life in patients with renal function impairment. Comedications that may affect renal function or result in significant hemodynamic change or interfere with disposition of metformin (eg, cationic drugs eliminated by renal tubular secretion) should be used with caution.

Hepatic Function

Avoid using metformin in patients with clinical or laboratory evidence of hepatic disease.

Change in clinical status

Promptly evaluate patients with type 2 diabetes previously well controlled on metformin who develop lab abnormalities or critical illness for evidence of ketoacidosis or lactic acidosis.

GI symptoms

GI symptoms occurring after a patient is stabilized on metformin are unlikely to be drug related, but could be because of lactic acidosis or other serious disease.

Hypoxic states

CV collapse (shock) from whatever cause, acute CHF, acute MI, and other conditions characterized by hypoxemia have been associated with lactic acidosis and may cause prerenal azotemia.

Iodinated contrast media

Withhold metformin therapy at the time of or prior to the procedure; withhold for 48 h subsequent to the procedure and reinstate only after renal function has been reevaluated and found to be healthy.

Loss of blood glucose control

A temporary loss of glycemic control can occur in patients stabilized on metformin who are exposed to fever, infection, stress, surgery, or trauma.


Hold therapy in patients undergoing surgical procedure until oral intake has resumed and renal function has been documented to be healthy.

Vitamin B 12

A decrease in vitamin B 12 levels to subnormal may occur. Supplementation may be necessary.



Lactic acidosis

Abdominal distress, increased somnolence, malaise, myalgia, respiratory distress.

Patient Information

  • Explain name, action, and potential adverse reactions of drug, including risk of developing lactic acidosis.
  • Advise patient or caregiver to read patient information leaflet before using the first time and with each refill.
  • Advise patient to take prescribed dose with food to decrease GI adverse reactions.
  • Advise patient using ER tablets to swallow tablets whole. Caution patient not to crush, chew, or break the tablets.
  • Inform patient using ER tablets that the inactive ingredients in the tablet may be eliminated in the feces as a soft mass that may look like the original tablet. Advise patient that the active medication will have already been absorbed into the body.
  • Advise patient that medication will be started at a low dose that may be gradually increased until max benefit is obtained.
  • Educate patient or caregiver regarding type 2 diabetes and its management, including target ranges for blood sugar control. Instruct patient that metformin is not a substitute for diet and exercise and to continue to follow prescribed regimens.
  • Educate patient or caregiver regarding potential long-term complications of uncontrolled diabetes and the need for regular general physical and eye examinations.
  • Emphasize the importance of regular daily blood glucose monitoring and periodic hemoglobin A 1c tests.
  • Advise patient to keep a log of measured blood sugars and to take it to each visit with their health care provider.
  • Advise patient to carry medical identification (eg, card, bracelet) of diabetes.
  • Caution patient to avoid excessive alcohol intake to reduce risk of developing lactic acidosis.
  • Inform patient that medication may cause an unpleasant metallic taste when it is first started but that this usually goes away with continued treatment. Advise patient to inform health care provider if this occurs and does not go away.
  • Advise patient that GI symptoms (eg, abdominal discomfort, diarrhea, gas, indigestion, nausea) are common when metformin is first started and during dose adjustments, but that they are temporary and go away. Caution patient that onset of GI symptoms developing late in therapy may indicate a serious condition (eg, lactic acidosis) and should be reported to health care provider immediately.
  • Instruct patient to report any of the following to health care provider immediately: feeling cold, dizzy, or light-headed; feeling very weak, tired, or uncomfortable; general body discomfort; slow or irregular heartbeat; unexplained muscle aches; unexplained rapid breathing or shortness of breath; unusual or unexpected stomach discomfort.
  • Inform patient that metformin alone usually does not cause hypoglycemia, but it may occur when used in combination with other medicines to treat diabetes.
  • Review symptoms of hypoglycemia and hyperglycemia and action plans to undertake in the event either occurs.
  • Instruct patient to notify health care provider if experiencing hypoglycemic episodes or if measured blood sugars are outside target range.

Copyright © 2009 Wolters Kluwer Health.