Starting Dose of Metformin
The recommended starting dose of metformin is 500 mg orally once or twice daily with meals, regardless of other medications the patient is taking. 1
Initial Dosing Strategy
Start with 500 mg once daily or twice daily with meals to minimize gastrointestinal side effects, which are the most common adverse effects limiting metformin use 2, 3, 1
The FDA-approved immediate-release formulation can be initiated at either 500 mg twice daily or 850 mg once daily, though the lower 500 mg dose is preferred for tolerability 1
For extended-release (ER) formulations, initiate at 500 mg once daily with the evening meal, which allows for 24-hour glucose control with a single dose 3
Titration Protocol
Increase the dose gradually by 500 mg increments every 7 days based on glycemic control and tolerability, up to a maximum of 2550 mg per day for immediate-release formulations 3, 1
For extended-release metformin, titrate by 500 mg weekly until reaching the target dose of 1000-2000 mg once daily 3
If gastrointestinal side effects occur during titration, decrease to the previous lower dose and attempt to advance at a later time 3
The typical effective dose range is 1000-2000 mg daily, with doses above 2000 mg potentially better tolerated when given three times daily with meals 1
Critical Renal Function Considerations
Before initiating metformin, assess renal function (eGFR) as this is the primary determinant of safe dosing:
Do not initiate metformin if eGFR is <45 mL/min/1.73 m² 2, 1
Metformin is contraindicated if eGFR is <30 mL/min/1.73 m² 2, 3, 1
For patients with eGFR 45-59 mL/min/1.73 m², standard dosing can be initiated but consider dose reduction in those at high risk for lactic acidosis 3
For patients with eGFR 30-44 mL/min/1.73 m², if already on metformin, reduce the total daily dose to 1000 mg (half the standard dose) 3
Drug Interaction Considerations
The starting dose of metformin does not change based on concomitant medications, as metformin does not undergo hepatic metabolism and has minimal drug-drug interactions 4
However, monitor glucose more closely if the patient is taking insulin or sulfonylureas, as these combinations increase hypoglycemia risk (though metformin itself does not cause hypoglycemia) 2
Metformin should be temporarily discontinued before procedures using iodinated contrast in patients with eGFR 30-60 mL/min/1.73 m², or in those with liver disease, alcoholism, or heart failure 3, 1
Formulation Selection
Extended-release formulations improve gastrointestinal tolerability and allow once-daily dosing, which may enhance adherence 3, 5
Extended-release metformin provides similar efficacy to immediate-release at comparable total daily doses, with the advantage of simplified dosing 5, 6
Patients who cannot tolerate immediate-release metformin due to GI side effects often tolerate the extended-release formulation better 5
Common Pitfalls to Avoid
Do not start at maximum doses – this dramatically increases GI intolerance and leads to discontinuation 3, 1
Do not forget to assess renal function before initiation – this is the most critical safety consideration to prevent lactic acidosis 1, 7
Do not delay dose titration unnecessarily – gradual weekly increases are safe and help achieve glycemic targets more quickly 3, 1
Monitor vitamin B12 levels periodically, especially in patients treated for more than 4 years or those with anemia or peripheral neuropathy 3