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· Decreases intestinal glucose absorption.

· Increases sensitivity to insulin.

Therapeutic Effects: 

· Maintenance of blood glucose.

Distribution: Enters breast milk in concentrations similar to plasma.

Metabolism/Excretion: Eliminated almost entirely unchanged by the kidneys.

Half-life: 17.6 hr.

· Hypersensitivity

· Metabolic acidosis

· Dehydration, sepsis, hypoxemia, hepatic impairment, excessive alcohol use (acute or chronic)

· Renal dysfunction (SCr >1.5 mg/dL in men or >1.4 mg/dL in women)

· Radiographic studies requiring IV iodinated contrast media (withhold metformin)

· HF.

Use Cautiously in: 

· Concurrent renal disease

· Geri: Geriatric/debilitated patients ( doses may be required; avoid in patients >80 yr unless renal function is normal)

· Chronic alcohol use/abuse

· Serious medical conditions (MI, stroke)

· Patients undergoing stress (infection, surgical procedures)

· Hypoxia

· Pituitary deficiency or hyperthyroidism

· OB: Lactation: Pedi: Pregnancy, lactation, or children <10 yr (safety not established; extended release for use in patients >17 yr only).

F and E: LACTIC ACIDOSIS.

Misc: decreased vitamin B12 levels.

· Acute or chronic alcohol ingestion or iodinated contrast media risk of lactic acidosis.

· Amiloride, digoxin, morphine, procainamide, quinidine, ranitidine, triamterene, trimethoprim, calcium channel blockers, and vancomycin may compete for elimination pathways with metformin. Altered responses may occur.

· Cimetidine and furosemide may  effects of metformin.

· Nifedipine absorption and effects.

Drug-Natural Products: 

· Glucosamine may worsen blood glucose control.

· Chromium, and coenzyme Q-10 may produce hypoglycemic effects.

· PO (Children >10 yr): 500 mg twice daily, may be  by 500 mg/day at 1-wk intervals, up to 2000 mg/day in 2 divided doses.

· Patients stabilized on a diabetic regimen who are exposed to stress, fever, trauma, infection, or surgery may require administration of insulin. Withhold metformin and reinstitute after resolution of acute episode.

· Metformin should be temporarily discontinued in patients requiring surgery involving restricted intake of food and fluids. Resume metformin when oral intake has resumed and renal function is normal.

· Withhold metformin before or at the time of studies requiring IV administration of iodinated contrast media and for 48 hr after study.

· PO: Administer metformin with meals to minimize GI effects.

· XR tablets must be swallowed whole; do not crush, dissolve, or chew.

Pharmacologic Classification: biguanides

· Tablets: 500 mg; 850 mg; 1000 mg;

· Cost: Generic— 500 mg; $6.99/100 850 mg; $7.18/100 1000 mg; $7.01/100.

· Extended-release tablets (Fortamet, Glucophage XR, Glumetza): 500 mg; 750 mg; 1000 mg;

· Cost: Generic— 500 mg; $74.50/100 750 mg; $119.70/100.

· Oral solution (Riomet) (cherry flavor): 100 mg/mL;

· Cost: $59.30/118 mL.

· In combination with:  glyburide (Glucovance) glipizide (Metaglip), pioglitazone (Actoplus Met, Actoplus Met XR), repaglinide (PrandiMet), rosiglitazone (Avandamet), alogliptin (Kazano), sitagliptin (Janumet, Janumet XR), saxagliptin (Kombiglyze XR), linagliptin (Jentadueto), canagliflozin (Invokamet), and dapagliflozin (Xigduo XR). See Appendix [not included in this PDA edition].

· Patients who have been well controlled on metformin who develop illness or laboratory abnormalities should be assessed for ketoacidosis or lactic acidosis. Assess serum electrolytes, ketones, glucose, and, if indicated, blood pH, lactate, pyruvate, and metformin levels. If either form of acidosis is present, discontinue metformin immediately and treat acidosis.

Lab Test Considerations: 

· Monitor serum glucose and glycosylated hemoglobin periodically during therapy to evaluate effectiveness of therapy. May cause false-positive results for urine ketones.

· Assess renal function before initiating and at least annually during therapy. Discontinue metformin if renal impairment occurs.

· Monitor serum folic acid and vitamin B12 every 1–2 yr in long-term therapy. Metformin may interfere with absorption.

· Noncompliance (Patient/Family Teaching).

· Explain to patient that metformin helps control hyperglycemia but does not cure diabetes. Therapy is usually long term.

· Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hyperglycemic or hypoglycemic episodes.

· Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 tsp of sugar, honey, or corn syrup dissolved in water, and notify health care professional.

· Instruct patient in proper testing of blood glucose and urine ketones. These tests should be monitored closely during periods of stress or illness and health care professional notified if significant changes occur.

· Explain to patient the risk of lactic acidosis and the potential need for discontinuation of metformin therapy if a severe infection, dehydration, or severe or continuing diarrhea occurs or if medical tests or surgery is required. Symptoms of lactic acidosis (chills, diarrhea, dizziness, low BP, muscle pain, sleepiness, slow heartbeat or pulse, dyspnea, or weakness) should be reported to health care professional immediately.

· Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications or alcohol.

· Inform patient that metformin may cause an unpleasant or metallic taste that usually resolves spontaneously.

· Inform patients taking XR tablets that inactive ingredients resembling XR tablet may appear in stools.

· Advise patient to inform health care professional of medication regimen before treatment or surgery.

· Advise patient to report the occurrence of diarrhea, nausea, vomiting, and stomach pain or fullness to health care professional.

· Insulin is the recommended method of controlling blood glucose during pregnancy. Counsel female patients to use a form of contraception other than oral contraceptives and to notify health care professional promptly if pregnancy is planned or suspected, or if breast feeding.

· Advise patient to carry a form of sugar (sugar packets, candy) and identification describing disease process and medication regimen at all times.

· Emphasize the importance of routine follow-up exams and regular testing of blood glucose, glycosylated hemoglobin, renal function, and hematologic parameters.