What is the recommended starting dose and 30‑day supply of metformin for an adult with type 2 diabetes who has adequate renal function (estimated glomerular filtration rate ≥ 45 mL/min/1.73 m²) and no contraindications?

Starting Dose of Metformin for a 30-Day Prescription

For an adult with type 2 diabetes and adequate renal function (eGFR ≥45 mL/min/1.73 m²), start metformin immediate-release at 500 mg orally twice daily with meals, or 850 mg once daily with a meal, providing a 30-day supply of either 60 tablets (500 mg) or 30 tablets (850 mg). 1

Initial Dosing Algorithm

Immediate-Release Metformin:

• Starting dose: 500 mg twice daily OR 850 mg once daily, both taken with meals 1
• 30-day supply: 60 tablets of 500 mg (if dosing twice daily) or 30 tablets of 850 mg (if dosing once daily) 1
• The 500 mg twice daily regimen is generally preferred as it causes fewer gastrointestinal side effects while allowing for more gradual titration 1

Extended-Release Metformin:

• Starting dose: 500 mg once daily with the evening meal 1
• 30-day supply: 30 tablets of 500 mg 1

Titration Schedule After Initial 30 Days

• For immediate-release: Increase by 500 mg weekly or 850 mg every 2 weeks based on glycemic control and tolerability 1
• For extended-release: Increase by 500 mg weekly 1
• Maximum dose: 2550 mg/day for immediate-release (though doses above 2000 mg are better tolerated when given three times daily with meals) 1

Mandatory Pre-Prescription Requirements

Check eGFR before initiating metformin: 1

• eGFR ≥60 mL/min/1.73 m²: Standard dosing as above, monitor annually 2
• eGFR 45-59 mL/min/1.73 m²: Can initiate at standard starting dose, but monitor every 3-6 months 2
• eGFR 30-44 mL/min/1.73 m²: Do NOT initiate metformin 1
• eGFR <30 mL/min/1.73 m²: Absolute contraindication 1

Critical Safety Considerations

Renal function monitoring frequency: 2

• eGFR ≥60: At least annually 2
• eGFR 45-59: Every 3-6 months 2
• eGFR 30-44: Every 3-6 months (if already on metformin at reduced dose) 2

Vitamin B12 monitoring: 2

• Check vitamin B12 levels if the patient has been on metformin for more than 4 years, as approximately 7% develop deficiency 2

Common Prescribing Pitfalls to Avoid

Do not use serum creatinine alone: 3

• Always calculate eGFR using the CKD-EPI equation rather than relying on serum creatinine cutoffs, as creatinine-based thresholds are outdated and can lead to inappropriate discontinuation, especially in elderly or small-statured patients 3

Do not initiate in borderline renal function: 1

• The FDA explicitly states that initiation is not recommended when eGFR is between 30-45 mL/min/1.73 m², even though continuation at reduced doses may be acceptable for patients already on metformin 1

Counsel on temporary discontinuation scenarios: 3

• Instruct patients to hold metformin during acute illness causing volume depletion (severe diarrhea, vomiting, fever), hospitalization with acute kidney injury risk, or before iodinated contrast procedures if eGFR is 30-60 mL/min/1.73 m² or if they have liver disease, alcoholism, or heart failure 3

Combination Therapy Considerations

Most patients benefit from dual therapy: 2

• Current KDIGO guidelines recommend that most patients with type 2 diabetes and eGFR ≥30 mL/min/1.73 m² benefit from treatment with both metformin AND an SGLT2 inhibitor from the outset 2
• This represents a shift from traditional stepwise therapy and should be considered even for initial prescriptions 2