What is the starting dose of metformin (biguanide oral hypoglycemic agent) for an adult patient with type 2 diabetes mellitus?

Starting Dose for Metformin

For immediate-release metformin, start with 500 mg orally twice daily with meals OR 850 mg once daily with meals; for extended-release metformin, start with 500 mg once daily with the evening meal. 1

Immediate-Release Formulation

• The FDA-approved starting dose is 500 mg twice daily or 850 mg once daily, both taken with meals. 1
• Titrate upward by 500 mg weekly or 850 mg every 2 weeks based on glycemic control and tolerability, up to a maximum of 2550 mg per day in divided doses. 1
• Doses above 2000 mg daily may be better tolerated when given three times daily with meals. 1
• The KDIGO guidelines align with this approach, recommending initial dosing of 500 mg or 850 mg once daily, with titration upward by 500 mg/day or 850 mg/day every 7 days until the maximum dose is reached. 2

Extended-Release Formulation

• Start with 500 mg once daily, preferably with the evening meal. 3, 1
• Increase by 500 mg increments every 7 days until the target dose is reached, with a maximum of 2000 mg daily. 2, 3
• Extended-release formulations provide similar efficacy to immediate-release metformin at comparable total daily doses but with once-daily administration, improving adherence. 3
• The extended-release formulation may offer better gastrointestinal tolerability compared to immediate-release, particularly for patients who experience GI side effects. 4, 5

Key Dosing Principles

• Always initiate at the lower starting dose to minimize gastrointestinal side effects (diarrhea, nausea, vomiting), which are the most common adverse effects limiting metformin use. 3, 4
• Gradual dose titration is essential—increasing too rapidly increases the risk of GI intolerance. 3
• Most patients achieve adequate glycemic control at 1000-2000 mg daily. 3, 5

Renal Function Considerations Before Initiation

• Check eGFR before starting metformin—do not initiate if eGFR is <45 mL/min/1.73 m². 2, 3, 1
• Metformin is contraindicated if eGFR is <30 mL/min/1.73 m². 2, 1
• For patients with eGFR ≥60 mL/min/1.73 m², use standard dosing without adjustment. 2, 3

Pediatric Dosing (Age 10 and Older)

• Start with 500 mg twice daily with meals. 1
• Increase in 500 mg weekly increments based on glycemic control and tolerability, up to a maximum of 2000 mg daily in divided doses. 1

Common Pitfalls to Avoid

• Do not start with higher doses (e.g., 1000 mg twice daily) in treatment-naive patients—this dramatically increases GI side effects and leads to discontinuation. 3, 4
• If GI side effects occur during titration, decrease to the previous lower dose and attempt to advance at a later time. 3
• Do not forget to assess renal function before initiation—starting metformin in patients with unrecognized renal impairment increases the risk of lactic acidosis. 2, 1
• Monitor eGFR at least annually in patients with normal renal function, and every 3-6 months when eGFR is <60 mL/min/1.73 m². 2, 3