Metformin in peritoneal dialysis patients — more benefit or risk?

Abstract

Contrary to previous precautions, metformin has been recently recommended in patients with diabetes complicated by moderate chronic kidney disease (eGFR 30–60 mL/min/1.73 m²). This resulted from studies that showed improved survivals with metformin treatment also in this population, and negligible risk of lactic acidosis with dosing reduction and adherence to known contraindications. Recently, metformin use has been advocated in patients with end-stage renal disease, including those treated with peritoneal dialysis. Beneficial effects of the drug on cardiovascular system speak in favor of its applicability — alleviation of cardiac ischemia-reperfusion injury and hypertrophy, as well as improvement of endothelial function, among others. On the other hand, metformin-induced enhancement of cellular catabolism seems to counter the concept. This latter impact, which is desired in patients with obesity and metabolic syndrome, may be harmful in those affected with end-stage kidney disease, whose increased mortality results largely from protein-energy wasting. Metformin might be rather useful in certain subgroups of this population, like patients at high risk of or with cancer, or female patients with ovulation disorders, given favorable effects of the drug in these conditions. Nevertheless, the risk of lactic acidosis due to metformin accumulation in settings of end-stage kidney failure overlapped with acute disorders diminishing oxidative metabolism, warrants further studies of the drug pharmacodynamics before it can be allowed in these patients.