Metformin and patients on dialysis

I enjoyed reading the concise, well-referenced summary on prescribing for patients on dialysis.¹ However, the statement ‘Metformin is contraindicated due to the risk of lactic acidosis’ is not referenced and is perhaps not supported by the available evidence.

A Cochrane review on the risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes concluded that there is no evidence at present that metformin is associated with an increased risk for lactic acidosis when prescribed under the study conditions.² The authors commented that of the 334 prospective studies, 143 (53%) allowed for the inclusion of renal insufficiency, following 37 360 patient-years of metformin use. One trial in the review questioned the standard contraindications by studying 393 patients, all with at least one contraindication to metformin use, and found no cases of lactic acidosis over four years.³ All of the patients had renal insufficiency, with mean plasma creatinine concentrations of 1.5–2.5 mg/dL (mean 1.8 mg/dL).

A review of metformin in chronic kidney disease nicely summarises the issue.⁴ It cites two small studies of metformin use in dialysis patients and recommends 250 mg daily for peritoneal dialysis patients and 500 mg after each dialysis session for those receiving haemodialysis.

Metformin is renally excreted and in overdose has been seen to cause lactic acidosis without other contributory comorbidity. While there are grounds for caution in patients on dialysis, an increased risk of lactic acidosis has not been specifically established. Many renal physicians choose to administer metformin in reduced doses to selected patients with end-stage renal disease because of its proven efficacy in the management of overweight patients with type 2 diabetes.

Brendan Smyth, Ceridwen Jones and John Saunders, the authors of the article, comment:

We thank Dr Richards for his comments which highlight the growing interest in extending the use of metformin to patients with moderate to severe chronic kidney disease. Within the constraints of our brief review we preferred to adhere to a conservative recommendation regarding metformin use in end-stage renal disease without describing the current controversy. We agree that recent studies have substantially altered our understanding of the risk–benefit profile of metformin in patients with chronic kidney disease and we look forward to larger studies with substantial follow-up of safety end points. However, until these are available we would continue to suggest that metformin not be used in dialysis patients except under the close supervision of a nephrologist or as part of a clinical trial.