Metformin Dosage for PCOS
For patients with PCOS, initiate metformin at 1.5-2g daily (the evidence-based target dose), starting with 500mg twice daily and titrating up over several weeks to minimize gastrointestinal side effects, with the goal of reaching the full therapeutic dose of 1500-2000mg daily. 1, 2
Starting and Target Dosing
Begin with 500mg orally twice daily with meals, then increase in 500mg weekly increments based on tolerability up to the target dose of 1500-2000mg daily. 1, 3
The typical effective dosing range for PCOS is 1.5 to 2g daily (1500-2000mg), which can be administered as 500mg three times daily or 850mg twice daily. 1, 2
Maximum dose is 2550mg per day in divided doses, though doses above 2000mg may be better tolerated when given three times daily with meals. 3
Extended-release formulations can be used if gastrointestinal side effects limit tolerability with immediate-release metformin, allowing for twice-daily dosing that may improve adherence. 1
Dose-Response Considerations
Higher doses (1700mg) are not more effective than standard doses (1000-1500mg) for most PCOS patients with normal to moderately elevated BMI. 4
However, obese patients (BMI >31) may require higher doses (2500mg daily) to achieve normalization of insulin resistance (HOMA index) and optimal metabolic response. 5
Patients with both hyperinsulinemia and hyperandrogenism show the greatest response to metformin, making these features important indicators for treatment selection. 6
Mandatory Pre-Treatment Assessment
Check baseline renal function (creatinine, eGFR) before initiating metformin, as it is absolutely contraindicated with eGFR <30 mL/min/1.73m² and initiation is not recommended with eGFR 30-45 mL/min/1.73m². 2, 3
Screen for hepatic disease, as known liver disease is an absolute contraindication. 2
Assess for alcohol abuse, hypoxemic conditions, and severe infections, all of which contraindicate metformin use. 1, 7
Clinical Monitoring and Expected Outcomes
Assess treatment response at 12-16 weeks, as this is the standard timeframe used in clinical studies evaluating metabolic and hormonal parameters in PCOS. 7
Expected benefits include improved menstrual cyclicity (66-100% of patients), reduced testosterone levels, decreased LDL cholesterol and triglycerides, and improved insulin sensitivity. 1, 8
Even modest weight loss of 5% enhances metformin's metabolic and reproductive effects, so concurrent lifestyle modification is essential. 7, 2
Critical Safety Precautions
Discontinue metformin during acute illness with dehydration or hypoxemia, as these conditions increase lactic acidosis risk. 7
Stop metformin at the time of iodinated contrast imaging procedures in patients with eGFR 30-60 mL/min/1.73m², and re-evaluate renal function 48 hours post-procedure before restarting. 7, 3
Provide contraception counseling to women of childbearing age, as metformin may normalize ovulation and increase risk of unplanned pregnancy. 1, 7
Managing Gastrointestinal Side Effects
Dose titration and extended-release formulations prevent premature discontinuation due to GI disturbances, the most common side effect limiting tolerability. 1, 7
Starting with lower doses (500mg once or twice daily) and gradually increasing over 2-4 weeks significantly improves tolerability. 3
Escalation Strategy for Inadequate Response
- If after 3-6 months of metformin plus lifestyle intervention there is inadequate response (defined as <5% weight loss or persistent metabolic dysfunction), consider adding a GLP-1 receptor agonist like semaglutide for additional metabolic benefits. 2