What are the uses, dosage, and guidelines for Metformin (Biguanide)?

From the Guidelines

Metformin is a first-line medication for treating type 2 diabetes, and its use is recommended for patients with an estimated glomerular filtration rate (eGFR) ≥30 ml/min per 1.73 m2, with a starting dose of 500 mg or 850 mg once daily, and titrated upwards by 500 mg/d or 850 mg/d every 7 days until maximum dose, as stated in the KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease 1.

Key Points

• Metformin should be used with caution in patients with kidney disease, and the dose should be adjusted based on the eGFR level.
• The medication should be started at a low dose and gradually increased to minimize gastrointestinal side effects.
• Patients should be monitored for vitamin B12 deficiency, especially those with anemia or peripheral neuropathy.
• Metformin should be temporarily discontinued before procedures using contrast dye and in situations of severe illness, dehydration, or liver disease to prevent lactic acidosis.

Dosage and Administration

• Initial dose: 500 mg or 850 mg once daily
• Titration: increase by 500 mg/d or 850 mg/d every 7 days until maximum dose
• Maximum dose: 2000-2500 mg daily divided into two or three doses
• Extended-release formulation: can be taken once daily, usually with the evening meal

Monitoring and Precautions

• Monitor eGFR regularly, at least annually or every 3-6 months
• Monitor vitamin B12 levels, especially in patients with anemia or peripheral neuropathy
• Temporarily discontinue metformin before procedures using contrast dye and in situations of severe illness, dehydration, or liver disease
• Inform healthcare providers about all medications being taken to avoid potential interactions

Side Effects

• Common side effects: diarrhea, nausea, abdominal discomfort
• Rare but serious side effect: lactic acidosis

Special Considerations

• Metformin may be safely used in patients with an estimated glomerular filtration rate as low as 30 mL/min/1.73 m2, but the dose should be adjusted based on the eGFR level 1.
• The medication should be used with caution in patients with kidney disease, and the dose should be adjusted based on the eGFR level.

From the FDA Drug Label

1 INDICATIONS AND USAGE

Metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus.

2 DOSAGE AND ADMINISTRATION

2.1 Adult Dosage The recommended starting dose of metformin hydrochloride tablets are 500 mg orally twice a day or 850 mg once a day, given with meals. Increase the dose in increments of 500 mg weekly or 850 mg every 2 weeks on the basis of glycemic control and tolerability, up to a maximum dose of 2550 mg per day, given in divided doses. Doses above 2000 mg may be better tolerated given 3 times a day with meals.

2.2 Pediatric Dosage for metformin hydrochloride tablets The recommended starting dose of metformin hydrochloride tablets for pediatric patients 10 years of age and older is 500 mg orally twice a day, given with meals. Increase dosage in increments of 500 mg weekly on the basis of glycemic control and tolerability, up to a maximum of 2000 mg per day, given in divided doses twice daily.

The uses of Metformin (Biguanide) are to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus as an adjunct to diet and exercise 2 2. The dosage guidelines are as follows:

• Adults: starting dose of 500 mg orally twice a day or 850 mg once a day, increasing up to a maximum dose of 2550 mg per day.
• Pediatric patients 10 years of age and older: starting dose of 500 mg orally twice a day, increasing up to a maximum of 2000 mg per day. The guidelines for use include:
• Assessing renal function prior to initiation and periodically thereafter.
• Discontinuing metformin hydrochloride tablets at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m^2 or other specified conditions.

From the Research

Uses of Metformin

• Metformin is used as a first-line pharmacotherapy to treat people with type 2 diabetes 3
• It is used to lower blood glucose concentration by decreasing hepatic glucose output and enhancing insulin sensitivity 3
• Metformin can be used to treat other conditions such as obesity, gestational diabetes, and polycystic ovary syndrome 4
• It has been shown to have a pleiotropic activity and favorable effect in different pathological conditions, including prediabetes, type 1 diabetes mellitus, and gestational diabetes mellitus 5

Dosage and Guidelines

• The dosage of metformin is not specified in the provided studies, but it is recommended as a first-line therapy for type 2 diabetes 3, 6, 4
• The American Diabetes Association recommends metformin as first-line therapy, but does not give exact specifications for second- and third-line agents 7
• Guidelines from the American College of Endocrinology and American Association of Clinical Endocrinologists recommend several options depending on the patient's hemoglobin A(1c) level 7
• Metformin can be used as monotherapy or in combination with other glucose-lowering therapies 3, 6

Benefits and Side Effects

• Metformin has been shown to have a substantial beneficial effect on cardiovascular disease outcomes, with a 36% relative risk reduction in all cause mortality and a 39% relative risk reduction in myocardial infarction 3
• It has been shown to be effective in lowering blood glucose levels without increasing the risk of hypoglycemia 4
• The most common side effects of metformin are gastrointestinal 3
• Metformin may also have cardioprotective and nephroprotective effects, and may possibly reduce the risk of cancer development, inhibit the incidence of neurodegenerative disease, and prolong the lifespan 5