What are the contraindications of metformin in patients with renal impairment?

Metformin is contraindicated in patients with severe renal impairment due to the increased risk of drug accumulation and lactic acidosis. However, evidence suggests that metformin can be used safely in patients with mild to moderate chronic kidney disease (CKD) (eGFR 30–60 mL/min/1.73 m²), as drug levels generally remain within the therapeutic range and the risk of lactic acidosis is not substantially increased in this group[1][3].

• Contraindications: Metformin should not be used in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) due to the risk of drug accumulation and lactic acidosis[1][3]. The context does not specify an absolute eGFR threshold, but severe impairment is generally defined as eGFR <30 mL/min/1.73 m².
• Cautions: In patients with mild to moderate CKD (eGFR 30–60 mL/min/1.73 m²), metformin can be used with dose adjustment and careful monitoring[1][3].
• Monitoring: Renal function (eGFR or creatinine clearance) should be assessed at baseline and at least annually, or more frequently in patients at increased risk of renal function decline[3]. Dose reduction is recommended as renal function decreases, and metformin should be discontinued if eGFR falls below 30 mL/min/1.73 m²[3].
• Lactic Acidosis Risk: The incidence of lactic acidosis in metformin users is low and comparable to the background rate in the general diabetic population, but risk increases with worsening renal function[1].
• Pharmacokinetics: Metformin is excreted unchanged in urine, and its clearance decreases proportionally with declining renal function, necessitating dose adjustment in renal impairment[3].

Note: The evidence is based on data up to 2014, and no randomized controlled trials have directly tested metformin safety in patients with severe CKD[1].