What is the initial recommended dose of metformin (biguanide) for a typical adult patient with type 2 diabetes mellitus?

Initial Metformin Dosing for Type 2 Diabetes

Start metformin at 500 mg once or twice daily with meals, then titrate by 500 mg weekly (or 850 mg every 2 weeks) up to a maximum effective dose of 2000 mg daily, divided into two doses. 1, 2

Starting Dose and Titration Strategy

• Begin with 500 mg once daily or twice daily with food to minimize gastrointestinal side effects, which are the most common adverse effects limiting metformin use 1, 3, 2
• The FDA label also permits starting with 850 mg once daily, though 500 mg is more commonly recommended to improve tolerability 2
• Increase by 500 mg increments weekly until reaching the target dose, based on glycemic control and tolerability 1, 3, 2
• Alternative titration: increase by 850 mg every 2 weeks if using the higher starting dose 2

Target Maintenance Dose

• The maximum effective dose is 2000 mg daily, typically given as 1000 mg twice daily with meals 1, 3
• The FDA label permits up to 2550 mg daily in divided doses, though doses above 2000 mg may be better tolerated when given three times daily with meals 2
• Most patients achieve adequate glycemic control at 2000 mg daily or less 1, 3

Critical Pre-Treatment Assessment

• Check estimated glomerular filtration rate (eGFR) before initiating metformin 1, 2
• Do not initiate metformin if eGFR is <45 mL/min/1.73 m² 3, 2
• Metformin is contraindicated if eGFR is <30 mL/min/1.73 m² 1, 2

Renal Function-Based Dosing Adjustments

For patients already on metformin whose renal function declines:

• eGFR ≥60 mL/min/1.73 m²: Continue standard dosing up to 2000 mg daily 1, 3
• eGFR 45-59 mL/min/1.73 m²: Consider dose reduction in patients at high risk of lactic acidosis (those with liver disease, heart failure, or conditions causing hypoperfusion) 1, 3
• eGFR 30-44 mL/min/1.73 m²: Reduce dose to 1000 mg daily (half the standard dose) 1, 3
• eGFR <30 mL/min/1.73 m²: Discontinue metformin entirely 1, 2

Monitoring Requirements

• Monitor eGFR at least annually in patients with normal renal function 1, 3
• Increase monitoring frequency to every 3-6 months once eGFR falls below 60 mL/min/1.73 m² 1, 3
• Consider periodic vitamin B12 level testing, especially in patients with anemia, peripheral neuropathy, or those treated for more than 4 years 1, 3

Common Pitfalls and How to Avoid Them

• Starting at too high a dose causes intolerable GI side effects: Always start at 500 mg and titrate gradually 1, 3
• If GI side effects occur during titration: Decrease to the previous lower dose and attempt to advance again later 3
• Consider extended-release formulation if immediate-release causes persistent GI symptoms, as it provides similar efficacy with once-daily dosing 3, 4, 5
• Temporarily discontinue metformin before iodinated contrast procedures in patients with eGFR 30-60 mL/min/1.73 m², or those with liver disease, alcoholism, or heart failure; restart 48 hours after procedure if renal function is stable 2
• Advise patients to stop metformin if they experience nausea, vomiting, or dehydration that could compromise renal function 1

Pediatric Dosing (Age ≥10 Years)

• Start with 500 mg twice daily with meals 2
• Increase in 500 mg weekly increments based on glycemic control and tolerability 2
• Maximum dose: 2000 mg daily in divided doses 1, 2