• Basic Info
• Top Questions
• Clinical Info
• Interactions

Cautions

Contraindications

• Sole therapy in patients with type 1 diabetes and in patients with diabetes complicated by acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma.
• Renal impairment (e.g., ≥1.5 or 1.4 mg/dL in men or women, respectively) or abnormal S_cr. Renal impairment may result from conditions such as cardiovascular collapse (shock), AMI, or septicemia.
• Congestive heart failure requiring drug therapy (e.g., digoxin, furosemide).
• Known hypersensitivity to metformin hydrochloride or any ingredient in the formulations.

Warnings/Precautions

Warnings

Lactic Acidosis

See Boxed Warning.

General Precautions

Hypoglycemia

Uncommon in patients receiving metformin as monotherapy. Debilitated, malnourished, or geriatric patients and patients with renal or hepatic impairment or adrenal or pituitary insufficiency may be particularly susceptible. Strenuous exercise, alcohol ingestion, insufficient caloric intake, or use in combination with other antidiabetic agents may increase risk. Hypoglycemia may be difficult to recognize in geriatric patients or in those receiving β-adrenergic blocking agents. (See Specific Drugs under Interactions.)

Hematologic Effects

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

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 and any abnormality properly investigated.

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).

Cardiovascular Effects

Possible increased cardiovascular mortality associated with other biguanide antidiabetic agents (i.e., phenformin). The American Diabetes Association (ADA) and other clinicians do not recommend changing current guidelines regarding the use of metformin as monotherapy or in combination with sulfonylureas pending the results of further studies of metformin alone or in combination with sulfonylureas.

Use of metformin in combination with rosiglitazone and insulin is not indicated; adverse cardiovascular events (e.g., edema, heart failure) have occurred with combined rosiglitazone and insulin therapy.

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.

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

Use of Fixed Combinations

When used in fixed combination with glipizide, glimepiride, or rosiglitazone, consider the cautions, precautions, and contraindications associated with the concomitant agent.

Specific Populations

Pregnancy

Category B.

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; not known if distributed into milk in humans. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy of metformin as conventional tablets or oral solution in children <10 years of age have not been established.

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

Safety and efficacy of metformin in fixed combination with glipizide or rosiglitazone in children have not been established. Data from a clinical trial in children 9–16 years of age comparing combined therapy with metformin and glyburide (Glucovance^®) with each drug as monotherapy did not reveal unexpected safety findings.

Geriatric Use

Insufficient number of geriatric patients in controlled clinical trials of metformin hydrochloride conventional (Glucophage^®) and extended-release tablets (Glucophage^® XR) to determine if such patients respond differently than younger adults. 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.

Use with caution, since renal function declines with age.

Monitor renal function periodically.

Do not initiate in patients ≥80 years of age without confirmation of adequate renal function as measured by Cl_cr.

Geriatric patients particularly susceptible to hypoglycemia, which may be difficult to recognize.

Renal Impairment

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., 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 evidence of renal impairment is present.

Patients whose serum creatinine concentrations exceed the upper limit of normal for their age should not receive metformin.

Hepatic Impairment

Avoid use. Elimination of lactate may be substantially reduced. (See Boxed Warning.)

Common Adverse Effects

Diarrhea, nausea, vomiting, abdominal bloating, abdominal cramping or pain, flatulence, anorexia.