Could metformin be used in patients with diabetes and advanced chronic kidney disease?

Abstract

Diabetes is an important cause of end stage renal failure worldwide. As renal impairment progresses, managing hyperglycaemia can prove increasingly challenging, as many medications are contra-indicated in moderate to severe renal impairment. Whilst evidence for tight glycaemic control reducing progression to renal failure in patients with established renal disease is limited, poor glycaemic control is not desirable, and is likely to lead to progressive complications. Metformin is a first-line therapy in patients with Type 2 diabetes, as it appears to be effective in reducing diabetes related end points and mortality in overweight patients. Cessation of metformin in patients with progressive renal disease may not only lead to deterioration in glucose control, but also to loss of protection from cardiovascular disease in a cohort of patients at particularly high risk. We advocate the need for further study to determine the role of metformin in patients with severe renal disease (chronic kidney disease stage 4-5), as well as patients on dialysis, or pre-/peri-renal transplantation. We explore possible roles of metformin in these circumstances, and suggest potential key areas for further study.

Metformin‐associated lactic acidosis: Moving towards a new paradigm?

“…Recent publications have advocated broadening the use of metformin in patients with more advanced CKD, including patients on dialysis and/or awaiting renal transplant. Treatment options for these patients are limited, and metformin has generally not been widely used for the reasons stated earlier.…”

Could metformin be used in patients with advanced chronic kidney disease?

“…We read with great interest the review article by Chowdhury et al Over the last 5 years there has been great interest in relaxing the contraindication of renal impairment for prescribing metformin . We have examined the use of metformin in patients with advanced chronic kidney disease (CKD) .…”

“…We have examined the use of metformin in patients with advanced chronic kidney disease (CKD) . Chowdhury et al referenced our publication of a population pharmacokinetic model, which we used to simulate possible dosing regimens for patients with all grades of renal function (down to creatinine clearances of 15 mL/min) . The goal of this analysis was to ensure that the 95th percentile peak plasma concentrations of metformin did not exceed 5 mg/L.…”

“…In addition to monitoring metformin plasma concentrations and renal function, a practice we and others encourage, we agree with the authors’ guidance on counselling patients with advanced CKD for “sick day rules.” One of the common signs patients reference prior to the onset of MALA is severe gastrointestinal symptoms (vomiting, diarrhoea) . This should be a red‐light warning for patients to cease metformin use and seek medical attention.…”

“…Chowdhury et al conclude that more studies examining the safety and efficacy of metformin in patients with advanced CKD are required. We have recently completed a small pharmacokinetic study on metformin in patients on chronic haemofiltration over 12 weeks.…”