Metformin (Glucophage)

pharmacology and clinical points about metformin (Glucophage)
Abdelwahab Ward, BS Pharm, PharmD
Antidiabetic, Biguanide
MECHANISM OF ACTIONã…¡ Decreases hepatic glucose production (gluconeogenesis) and increases peripheral glucose uptake (sensitizes peripheral tissue to insulin). Slows intestinal glucose absorption. Decreases fatty acid oxidation.

  • First line agent in type 2 diabetes mellitus patients (obese patients, hyperlipidemia and children over age 10 with type 2 diabetes.
  • Metabolic syndrome.
  • Polycystic ovary syndrome (PCOS).
  • Induces ovulation (with or without hyperandrogenism).
  • Other indications (Hemoglobin A1C < 9%, High fasting blood glucose 160-250 mg/dL and Dyslipidemia
  • Adults: 500 mg orally twice daily or 850 mg once daily. May increase 500 mg/week or 850 mg/2 weeks to maximum of 3000 mg/day in divided doses. Dosage should be adjusted based on response and blood glucose level. 
  • Glucophage XR tablets: initially, 1000 mg/day PO with evening meal. May be increased by 500 mg/week to a maximum of 2000 mg once daily (may increase to 2500 mg). If higher doses are required (3000 mg), use immediate-release tablets.
  • Pediatric patients 10–16 years: 500 mg twice daily with meals. May increase 500 mg/week to maximum of 2000 mg/day in divided doses. Glucophage XR tablet is not recommended.
  • Summary: (1) Dosing for immediate-release tablets, start IN WEEK 1 by 500 mg orally twice daily. IN WEEK 2, you can increase dose to 1000 mg orally qAM and 500 mg orally qPM OR 850 mg orally twice daily then IN WEEK 3 give 1000 mg orally twice daily. (2) Dosing for long acting metformin (Glucophage XR), start metformin XR 500 mg daily then increase by 500 mg weekly until at 2000 mg or at goal blood sugar. Dose may be divided to twice daily.
  • Risk of lactic acidosis ã…¡ Avoid in renal insufficiency, recent guidelines recommend to avoid if eGFR < 30 ml/min and reduce metformin dose to half if eGFR 30-50 mL/min. Older guidelines recommend to avoid if eGFR < 60 mL/min or avoid if serum creatinine > 1.5 mg/dL in men and > 1.4 mg/dL in women. Also avoid concurrent IV iodinated contrast dye use and allow 48 hour wash-out of dye, or confirm normal renal function tests after dye.
  • Avoid in hepatic insufficiency, also avoid if excessive alcohol.
  • Hold prior to iodinated contrast dye or surgery.
  • Avoid in proteinuria and peripheral vascular disease.
  • Not contraindicated in stable congestive heart failure.
  • Route: Oral.
  • Peak:2–2.5 hr.
  • Duration: 10–16 hr.
  • Metabolism: T1/2, 6.2 and 17.6 hr.
  • Distribution: Crosses placenta; enters breast milk.
  • Excretion: Urine.
  • Gastrointestinal side effects (up to one third of patients) include abdominal discomfort, diarrhea, metallic taste nausea or vomiting and anorexia. To prevent (improving compliance): (1) Expect gastrointestinal adverse effects to be transient (days to weeks). (2) Slow titration from 500 mg daily (or 250 mg) up to 2000 mg over 1-2 months. (3) Extended release formulations have less adverse effects (and may be divided twice daily). (4) Take during after a large meal.
  • Folic acid deficiency (decreased folic acid absorption).
  • Vitamin B12 deficiency (due to decreased absorption). For further information, see topic on Management of vitamin B12 deficiency. Consider periodic screening every 2-3 years in higher risk patients, such as proton pump inhibitor use, vegetarians and elderly. Check serum B12 when peripheral neuropathy occurs (don't assume diabetic nephropathy only). Recheck serum B12 if new numbness or paresthesias occur.
  • Risk of lactic acidosis (see contraindications above). Severe lactic acidosis may occur with acute overdose or in significantly reduced renal function.
Abdelwahab Ward, BS Pharm, PharmD