What is the recommended dose of metformin (Metformin Hydrochloride) SR (Sustained Release) for adults with type 2 diabetes?

Metformin SR Dosing for Type 2 Diabetes

For metformin extended-release (SR/XR), start with 500 mg once daily with the evening meal, then titrate upward by 500 mg weekly to a target dose of 1500-2000 mg once daily, with a maximum of 2000 mg daily. 1

Initial Dosing Strategy

• Start at 500 mg once daily with the evening meal to minimize gastrointestinal side effects 2, 3
• The evening dosing is preferred as it provides optimal 24-hour glucose control with peak plasma levels occurring 4-8 hours after administration 4
• Extended-release formulations allow once-daily dosing compared to twice-daily immediate-release metformin, improving adherence 3

Titration Protocol

• Increase by 500 mg increments every 7 days based on glycemic response and tolerability 2, 1
• The target effective dose is typically 1500-2000 mg once daily 3
• Maximum recommended dose for extended-release is 2000 mg daily (lower than the 2550 mg maximum for immediate-release) 1

Dose Adjustments Based on Kidney Function

Critical renal function thresholds require dose modification:

• eGFR ≥60 mL/min/1.73 m²: Continue standard dosing up to 2000 mg daily 2
• eGFR 45-59 mL/min/1.73 m²: Continue same dose but consider reduction in patients at high risk for lactic acidosis 2, 3
• eGFR 30-44 mL/min/1.73 m²: Reduce total daily dose to 1000 mg (half the standard dose) 2, 3
• eGFR <30 mL/min/1.73 m²: Stop metformin entirely; do not initiate 2, 1

Monitoring Requirements

Kidney function monitoring frequency:

• eGFR ≥60 mL/min/1.73 m²: Monitor at least annually 2, 3
• eGFR <60 mL/min/1.73 m²: Increase monitoring to every 3-6 months 2, 3

Vitamin B12 monitoring:

• Monitor for vitamin B12 deficiency in patients treated for more than 4 years, especially those with anemia or peripheral neuropathy 2, 3

Key Advantages of Extended-Release Formulation

• Reduced gastrointestinal side effects compared to immediate-release: only 3.3% of patients experience GI side effects with extended-release versus higher rates with immediate-release 5
• Achieves similar glycemic control with lower total daily doses compared to immediate-release formulations 6
• Once-daily dosing improves adherence with 83% of patients preferring extended-release over immediate-release 6
• Lower systemic metformin exposure while maintaining efficacy through enhanced gut-based mechanisms 7

Common Pitfalls to Avoid

Do not initiate metformin in patients with eGFR 30-45 mL/min/1.73 m² - this is explicitly not recommended, though continuation at reduced dose may be considered if already established 1

Discontinue before iodinated contrast procedures in patients with eGFR 30-60 mL/min/1.73 m², those with liver disease, alcoholism, or heart failure; restart only after confirming stable renal function 48 hours post-procedure 1

Ghost tablets in stool are commonly reported (54% of patients) with extended-release formulations and are benign - this represents the empty tablet shell and does not indicate malabsorption 6

Combination Therapy Context

• Metformin should be used as first-line therapy alongside an SGLT2 inhibitor for most patients with type 2 diabetes and eGFR ≥30 mL/min/1.73 m² 2
• Continue metformin when adding other agents, including insulin, as long as tolerated and not contraindicated 3
• If glycemic targets are not met after 3 months at maximum tolerated dose, add a GLP-1 receptor agonist as the preferred third agent 2