What is the creatinine level at which metformin (Metformin Hydrochloride) cannot be used due to Impaired Renal Function?

From the Guidelines

Metformin should not be used when the estimated glomerular filtration rate (eGFR) is below 30 mL/min/1.73m², as this increases the risk of lactic acidosis, a rare but potentially fatal complication of metformin therapy. The use of metformin in patients with chronic kidney disease (CKD) requires careful consideration of the potential risks and benefits. According to the most recent guidelines, metformin may accumulate with reduced kidney function and increase the risk for lactic acidosis, although this risk is very low in absolute terms 1.

Key Considerations

• The dose of metformin should be reduced when the eGFR is less than 45 mL/min/1.73 m2 (or 45 to 59 mL/min/1.73 m2 in some patients at high risk for acute kidney injury) 1.
• Metformin should be withdrawn when the eGFR is less than 30 mL/min/1.73 m2 or kidney failure develops 1.
• Regular monitoring of kidney function is essential for all patients on metformin, with more frequent monitoring recommended for those with borderline kidney function or risk factors for acute kidney injury 1.
• Metformin may cause vitamin B12 deficiency, and monitoring of levels is advised with long-term use (>4 years) 1.

Recommendations

• Avoid metformin in patients with eGFR < 30 mL/min/1.73m² due to the increased risk of lactic acidosis 1.
• Use metformin with caution in patients with moderate kidney impairment (eGFR 30-45 mL/min/1.73m²) and at reduced doses, typically not exceeding 1000 mg daily 1.
• Monitor kidney function regularly in patients on metformin, especially in those with borderline kidney function or risk factors for acute kidney injury 1.

From the FDA Drug Label

Metformin hydrochloride tablets are contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 Initiation of metformin hydrochloride tablets is not recommended in patients with eGFR between 30 to 45 mL/min/1. 73 m 2. The value of the creatinine that metformin cannot be used with is not directly provided, but eGFR values are given.

• An eGFR of less than 30 mL/min/1.73 m^2 is a contraindication for metformin use 2.
• An eGFR between 30 to 45 mL/min/1.73 m^2 is not recommended for metformin initiation 2 and 2. Note that creatinine levels are not explicitly mentioned in the provided text, but eGFR values are used to assess renal function.

From the Research

Metformin Contraindications

• The value of creatinine that metformin cannot be used with is equal to or above 1.4 and 1.5 mg/dL for women and men respectively 3.
• However, it is noted that creatinine is not the only surrogate of renal dysfunction, and formulas such as the MDRD and CKD-EPI are now used as the standard for renal function assessment 3.
• The use of metformin has been considered safe down to creatinine clearances of 30 mL/min/1.73 m2 3, 4.
• Prescribing metformin in people with severe renal impairment (eGFR < 30 mL/min/1.73m2) remains a controversial issue due to the observed increased risk of lactic acidosis and all-cause mortality 4.

Renal Function Markers

• Serum creatinine values alone would contraindicate metformin therapy in 12.4% of the study population, despite having a GFR greater than 30 mL/min/1.73 m2 3.
• The use of serum creatinine as the single marker for renal function would significantly reduce metformin eligibility 3.
• Estimated glomerular filtration rate (eGFR) is now considered a more accurate marker of renal function than serum creatinine alone 3, 5.

Safety of Metformin Use

• The overall incidence of lactic acidosis is estimated at an upper limit of eight cases per 100 000 patient-years 5.
• The reported incidence of lactic acidosis in clinical practice has proved to be very low (<10 cases per 100,000 patient-years) 6.
• Current renal function cutoffs for metformin may be too conservative, depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy 6.