What is the recommended dose of metformin (per kilogram of body weight) for an adult patient with type 2 diabetes mellitus and normal renal function?

Metformin Dosing Per Kilogram

Metformin is not dosed per kilogram of body weight in adults; instead, it is dosed based on absolute milligram amounts with titration according to glycemic control and renal function. 1

Standard Adult Dosing (Normal Renal Function)

For adults with type 2 diabetes and eGFR ≥60 mL/min/1.73 m², metformin dosing follows an absolute milligram-based approach rather than weight-based calculations:

Immediate-Release Formulation

• Starting dose: 500 mg orally twice daily OR 850 mg once daily, given with meals 1
• Titration: Increase by 500 mg weekly or 850 mg every 2 weeks based on glycemic control and tolerability 1
• Maximum dose: 2,550 mg/day in divided doses (though doses above 2,000 mg are better tolerated when given three times daily with meals) 1

Extended-Release Formulation

• Starting dose: 500 mg once daily 2
• Titration: Increase by 500 mg weekly until maximum dose is reached 2
• Maximum dose: 2,000-2,250 mg daily 2

The FDA label explicitly provides absolute dosing without any reference to body weight calculations, which is the standard of care for metformin therapy in adults 1. Research supports that therapeutic plasma concentrations range from 0.5-1.0 mg/L in the fasting state and 1-2 mg/L postprandially, achieved through these fixed-dose regimens rather than weight-based dosing 3.

Renal Function-Based Dose Adjustments

Critical caveat: Metformin dosing is primarily determined by renal function, not body weight, as the drug undergoes exclusive renal excretion without hepatic metabolism 3.

eGFR ≥60 mL/min/1.73 m²

• Continue standard dosing up to maximum recommended dose 4, 2
• Monitor kidney function at least annually 4

eGFR 45-59 mL/min/1.73 m²

• Continue current dose but consider reduction in high-risk patients (advanced age, liver disease, heart failure) 4, 2
• Maximum recommended dose: 1,700 mg daily 2
• Increase monitoring frequency to every 3-6 months 4

eGFR 30-44 mL/min/1.73 m²

• Reduce dose to half the maximum: typically 500-1,000 mg daily 4, 2
• Do NOT initiate metformin in this range 1
• Monitor kidney function every 3-6 months 4, 2

eGFR <30 mL/min/1.73 m²

• Metformin is contraindicated 4, 1
• Discontinue immediately 4, 2

Why Not Weight-Based Dosing?

The absence of per-kilogram dosing for metformin in adults reflects several pharmacokinetic principles:

• Metformin has an absolute oral bioavailability of 40-60% with saturable absorption kinetics, meaning higher doses show decreased relative absorption 3
• The drug does not bind to plasma proteins and is not metabolized, undergoing direct renal excretion 3
• Efficacy and safety are determined by plasma concentrations (target ~1 mg/L for efficacy, <3 mg/L steady-state and <5 mg/L peak for safety), which are achieved through fixed-dose titration rather than weight-based calculations 5, 3

Research analyzing metformin clearance demonstrates that renal function estimates (using Cockcroft-Gault, MDRD, or CKD-EPI equations) show strong correlation with metformin clearance (r² = 0.699-0.735), while body weight is not incorporated into standard dosing algorithms 5.

Additional Monitoring Requirements

• Vitamin B12 levels: Monitor in patients on metformin >4 years due to deficiency risk 4, 2
• "Sick day rules": Temporarily discontinue during serious intercurrent illness that increases acute kidney injury risk 2
• Contrast imaging: Discontinue in patients with eGFR 30-60 mL/min/1.73 m² or those with liver disease, alcoholism, or heart failure prior to iodinated contrast procedures; restart after 48 hours if renal function is stable 1

Pediatric Exception

Note: Pediatric patients (age 10 years and older) receive the same absolute dosing as adults: starting dose 500 mg twice daily, maximum 2,000 mg/day in divided doses 1. Even in children, weight-based dosing is not utilized.