What is the recommended dose and frequency of metformin (biguanide) for adults with type 2 diabetes mellitus?

From the Guidelines

The recommended starting dose of metformin for adults with type 2 diabetes is typically 500 mg taken orally once or twice daily with meals, or 850 mg once daily, as supported by the most recent guidelines 1. This dose should be gradually increased to minimize gastrointestinal side effects, with a common approach being to increase by 500 mg weekly until reaching the effective dose. The maximum recommended daily dose is generally 2,000-2,550 mg, divided into two or three doses per day. Extended-release formulations allow for once-daily dosing, usually with the evening meal. Some key points to consider when prescribing metformin include:

• Dose adjustments are necessary for patients with reduced kidney function, with metformin contraindicated when eGFR falls below 30 mL/min/1.73m² 1.
• Metformin works by decreasing hepatic glucose production, reducing intestinal glucose absorption, and improving insulin sensitivity.
• Common side effects include diarrhea, nausea, and abdominal discomfort, which often improve with time.
• Taking metformin with food helps minimize these gastrointestinal effects.
• Patients should be advised to maintain consistent carbohydrate intake throughout the day and monitor blood glucose regularly, especially when initiating therapy.
• Long-term use of metformin may cause vitamin B12 deficiency, and periodic testing of vitamin B12 levels should be considered in metformin users, especially those with anemia or peripheral neuropathy 1.

From the FDA Drug Label

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. The recommended dose and frequency of metformin for adults with type 2 diabetes mellitus is:

• Starting dose: 500 mg orally twice a day or 850 mg once a day, given with meals
• Dose increment: 500 mg weekly or 850 mg every 2 weeks
• Maximum dose: 2550 mg per day, given in divided doses
• Administration: given with meals 2

From the Research

Metformin Dose and Frequency

• The recommended dose and frequency of metformin for adults with type 2 diabetes mellitus is not explicitly stated in the provided studies 3, 4, 5, 6.
• However, a study published in 2021 7 examined metformin dosage patterns in type 2 diabetes patients in a real-world setting in the United States.
• The study found that 31.3% of patients received an initial daily metformin dose of <850 mg, 46.9% received 850-1499 mg, and 21.8% received ≥1500 mg 7.
• Additionally, 34.1% of patients received ≥1500 mg metformin daily at initiation or within six months after initiation 7.
• The study suggests that there is a need for efforts to maximize the proportion of eligible patients receiving a recommended metformin dose, and factors impacting metformin dosage could be useful guidance 7.

Factors Affecting Metformin Dosage

• Patient age, with those aged 65-79 years being less likely to receive ≥1500 mg metformin daily 7.
• Race, with blacks being less likely and Hispanics being more likely to receive ≥1500 mg metformin daily compared to whites 7.
• HbA1c levels before metformin initiation, with patients having higher HbA1c levels being more likely to receive ≥1500 mg metformin daily 7.

General Guidance on Metformin

• Metformin is usually the first-line pharmacotherapy for type 2 diabetes mellitus after lifestyle modification 3, 4.
• The evidence supports metformin as first-line therapy for type 2 diabetes, given its relative safety and beneficial effects on hemoglobin A1c, weight, and cardiovascular mortality (compared with sulfonylureas) 4.