Overview
Metformin is a first-line oral antihyperglycemic agent used to improve glycemic control in type 2 diabetes mellitus. It works primarily by decreasing hepatic glucose production and increasing insulin sensitivity in peripheral tissues. The drug is generally well-tolerated but carries a risk of lactic acidosis, particularly in patients with renal impairment.
Mechanism of Action
Metformin decreases hepatic glucose production, reduces intestinal glucose absorption, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. It activates AMP-activated protein kinase (AMPK), which plays a key role in cellular energy homeostasis.
Indications
- Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
- Adjunct to diet and exercise to improve glycemic control in pediatric patients 10 years and older with type 2 diabetes mellitus
Common Doses
- 500 mg
- 850 mg
- 1000 mg
Dosage
Typically initiated at 500 mg twice daily or 850 mg once daily with meals, titrated upward based on glycemic response. Maximum recommended daily dose is 2,550 mg for adults and 2,000 mg for pediatric patients. Extended-release formulations may be administered once daily.
Contraindications
- Severe renal impairment (eGFR below 30 mL/min/1.73 m²)
- Hypersensitivity to metformin
- Acute or chronic metabolic acidosis, including diabetic ketoacidosis
Side Effects
- Gastrointestinal: Diarrhea, nausea, vomiting, abdominal discomfort, flatulence
- Metabolic: Lactic acidosis (rare but serious)
- Hematologic: Vitamin B12 deficiency with long-term use
- Hypoglycemia (especially with concomitant insulin or sulfonylureas)
Interactions
- Carbonic anhydrase inhibitors (topiramate, zonisamide, acetazolamide): May increase risk of lactic acidosis
- Drugs that reduce metformin clearance (ranolazine, vandetanib, dolutegravir, cimetidine): May increase metformin exposure
- Alcohol: Potentiates metformin's effect on lactate metabolism
- Insulin secretagogues or insulin: May increase hypoglycemia risk
- Drugs affecting glycemic control (thiazides, corticosteroids, phenothiazines): May alter blood glucose control
Counseling Points
- Take with meals to minimize gastrointestinal side effects
- Report symptoms of lactic acidosis immediately: malaise, myalgia, respiratory distress, abdominal pain, hypothermia, bradycardia
- Avoid excessive alcohol consumption
- Monitor blood glucose regularly as directed
- Be aware of potential vitamin B12 deficiency with long-term use
- Inform healthcare provider of all medications, including over-the-counter drugs