Establishing pragmatic estimated GFR thresholds to guide metformin prescribing


: Professor Eric S. Kilpatrick MD FRCPath, Department of Clinical Biochemistry, Hull Royal Infirmary, Anlaby Road, Hull HU3 2JZ, UK. E-mail:


Aims  Renal impairment is a contraindication to metformin treatment because of the perceived increased risk of lactic acidosis. Current guidelines define renal impairment according to the serum creatinine of the individual, but this measure is being supplanted by the use of estimated glomerular filtration rate (eGFR) as it gives a closer estimate to true GFR. This study aimed to establish pragmatic eGFR limits for use in patients being considered for metformin treatment.

Methods  Estimated GFR measurements corresponding to currently used metformin creatinine limits of 130 and 150 µmol/l were derived and then applied to 12 482 patients with diabetes in Hull and East Yorkshire.

Results  Few patients with a serum creatinine of 130 or 150 µmol/l have an eGFR of < 30 ml/min/1.73 m2[chronic kidney disease (CKD) stage 4 or greater], while most are between 30 and 59 ml/min/1.73 m2 (CKD stage 3). When applied to the 12 482 patients (median age 67 years, interquartile range 56–75), males predominated when using creatinine cut-offs (13.6% of males and 8.3% of females had creatinine > 130 µmol/l; 8.2% males and 5.2% females > 150 µmol/l), but not using eGFR CKD thresholds (3.3% males and 4.7% females < 30 ml/min/1.73 m2; 20.8% males and 28.1% females eGFR 30–59 ml/min/1.73 m2). Similar proportions of patients as currently would have metformin withheld if using eGFR cut-offs between 30 and 49 ml/min/1.73 m2.

Conclusions  We have proposed pragmatic eGFR limits to guide metformin prescribing in patients with renal impairment. CKD stage 4 or greater should be an absolute contraindication to metformin, while CKD stage 3 should alert clinicians to consider other risk factors before initiating or continuing treatment.