Update on the Protective Renal Effects of Metformin in Diabetic Nephropathy

Background: Diabetic nephropathy is one of the most important complications in patients with diabetes mellitus. Main steps crucial for the pathogenesis of diabetic nephropathy involve amongst others the modulation of cell signaling via AMP-activated kinase (AMPK) and mammalian target of rapamycin (mTOR), reactive oxygen generation, and endoplasmic reticulum stress under diabetic or hyperglycemic conditions. These processes mediate increased loss of renal cells, such as podocytes, which consequentially leads to renal damage and loss of renal functions, such as structural integrity and glomerular filtration in diabetic nephropathy. The anti-diabetic drug metformin has been widely used for pharmacotherapeutic treatment of patients with diabetes mellitus. Besides its anti-diabetic actions, recent studies revealed additional nephroprotective effects of metformin in vitro and in vivo. Metformin was found to diminish apoptosis in different experimental renal settings. Moreover, it was shown to reduce albuminuria in diabetic rats as well as in patients with type 2 diabetes mellitus. These effects were demonstrated to be mediated via the AMPK/mTOR signaling axis. These data indicate beneficial and renoprotective effects of metformin in diabetic nephropathy. Objective: In this review, we will summarize the latest findings regarding the nephroprotective impact of metformin in vitro and in vivo. Moreover, we will depict and discuss the therapeutic potential of this drug for the treatment of diabetic nephropathy.