What it's for (Indications)
- Metformin is indicated for the management of Type 2 Diabetes Mellitus (maturity onset diabetes), either as monotherapy or in combination with sulfonylureas.
- It is also used as adjuvant therapy in insulin-dependent diabetes, particularly in obese patients, to improve glucose tolerance and lower both basal and postprandial plasma glucose.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | Metformin hydrochloride extended-release tablets should be swallowed whole and never crushed, cut, or chewed. The typical starting dose is 500 mg orally once daily with the evening meal. The dose can be increased by 500 mg weekly, up to a maximum of 2,000 mg once daily with the evening meal. Patients previously on metformin hydrochloride tablets may be switched to the extended-release formulation at the same total daily dose, not exceeding 2,000 mg once daily. Renal Function Assessment: Prior to initiation, assess renal function with estimated glomerular filtration rate (eGFR). Do not use in patients with eGFR below 30 mL/minute/1.73 m2. Initiation is not recommended in patients with eGFR between 30 to 45 mL/minute/1.73 m2. Assess risk/benefit of continuing if eGFR falls below 45 mL/minute/1.73 m2, and discontinue if eGFR falls below 30 mL/minute/1.73 m2. |
Safety & Warnings
Common Side Effects
- Common adverse reactions include gastrointestinal upset (e.
- g.
- , diarrhea, nausea/vomiting, abdominal pain, constipation, abdominal distention, dyspepsia/heartburn, flatulence), taste disturbance, dizziness, headache, and upper respiratory infection.
- Other reported side effects include abnormal liver function tests, hepatitis, skin reactions, reduced Vitamin B12 absorption, and rarely, hypoglycemia.
- The most severe, though rare, side effect is lactic acidosis.
Serious Warnings
- Black Box Warning: WARNING: LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally.
- Lactic Acidosis: There is a serious risk of lactic acidosis, which can be fatal.
- Risk factors for lactic acidosis must be assessed, and the drug should be discontinued immediately if metabolic acidosis is suspected.
- Avoid excess alcohol consumption, as it significantly increases the risk of lactic acidosis.
- Renal Impairment: Metformin should be used with caution in patients with kidney impairment.
- Renal function (eGFR) must be assessed prior to initiation and monitored at least annually.
- Initiation is not recommended if eGFR is between 30 to 45 mL/minute/1.
- 73 m2.
- If eGFR falls below 45 mL/minute/1.
- 73 m2, the risk/benefit of continuing treatment should be carefully assessed.
- The medicine must be discontinued if eGFR falls below 30 mL/minute/1.
- 73 m2.
- Liver Impairment: Use cautiously in patients with liver impairment; proper dose adjustment may be necessary, and abnormal liver function tests/hepatitis can occur.
- Vitamin B12 Deficiency: Metformin can cause reduced Vitamin B12 absorption.
- Hypoglycemia: May occur, particularly when used in combination with other antihyperglycemic agents.
- Pregnancy: Metformin is not recommended during pregnancy.
- Consult your doctor for more information.
- Lactation: Metformin is not recommended for nursing females.
- Consult your doctor for more information.
- Surgical Procedures and Iodinated Contrast Imaging: Discontinue the medicine for 48 hours before and after elective surgery or iodinated contrast imaging procedures.
- Driving: This medicine does not usually affect driving ability.
- However, if experiencing trouble, avoid driving and consult your doctor.
How it Works (Mechanism of Action)
Metformin is an antihyperglycemic agent that improves glucose tolerance in patients with type 2 diabetes mellitus. Its primary mechanisms of action include decreasing hepatic glucose production, reducing intestinal absorption of glucose, and enhancing insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged, while fasting insulin levels and day-long plasma insulin response may decrease.