Nephroprotective Effects of Metformin in Diabetic Nephropathy

Abstract

Metformin, a well-known anti-diabetic agent, is very effective in lowering blood glucose in patients with type 2 diabetes with minimal side-effects. Metformin is also being recommended in the treatment of obesity and polycystic ovary syndrome. Metformin elicits its therapeutic effects mainly via activation of AMP-activated kinase (AMPK) pathway. Renal cells under hyperglycemic or proteinuric conditions exhibit inactivation of cell defense mechanisms such as AMPK and autophagy, and activation of pathologic pathways such as mammalian target of rapamycin (mTOR), endoplasmic reticulum (ER) stress, epithelial-to-mesenchymal transition (EMT), oxidative stress, and hypoxia. As these pathologic pathways are intertwined with AMPK signaling, the potential benefits of metformin therapy in patients with type 2 diabetes would extend beyond its anti-hyperglycemic effects. However, since metformin is eliminated unchanged through the kidneys and some studies have shown the incidence of lactic acidosis with its use during severe renal dysfunction, the use of metformin was contraindicated in patients with renal disease until recently. With more studies indicating the relatively low incidence of lactic acidosis and revealing the additional benefits with metformin therapy, the US FDA has now approved metformin to be administered in patients with established renal disease based on their renal function. The purpose of this review is to highlight the various mechanisms by which metformin protects renal cells that have lost its functionality in a diabetic or non-diabetic setting and to enlighten the advantages and therapeutic potential of metformin as a nephroprotectant for patients with diabetic nephropathy and other non-diabetic forms of chronic kidney disease. J. Cell. Physiol. 232: 731-742, 2017. © 2016 Wiley Periodicals, Inc.

Survival benefits in colorectal adenocarcinoma with the use of metformin among a black diabetic inner city population

“…Collectively these data have been reflected in the recent US FDA recommendations for metformin use in patients with chronic kidney disease (CKD) including those with an eGFR between 30 and 45 ml/min/1.73 m 2 [34,35]. This ease on the restriction of metformin use has the potential of increasing the use of metformin that currently includes nearly 15 million patients with diabetes, thus providing more opportunities for cancer prevention, decrease cardiovascular disease and potential amelioration of CKD among DMs, a population that vulnerable to both CKD as well as malignancy [37]. …”

Mechanistic Insight and Management of Diabetic Nephropathy: Recent Progress and Future Perspective

“…In addition, there are two types of drugs commonly used in daily clinical aside from thiazolidinediones and sulfonylureas, metformin, and acarbose. They are distinguished very effectively in lowering blood glucose in patients with diabetes mellitus with minimal side-effects; besides, studies have found that metformin also could exert renoprotective properties owing to its multieffects on multiple signaling pathways apart from its use as an antidiabetic drug [42–44]. Taken together, despite the benefits derived from strict control of glucose, many patients continue to enter into ESRD.…”

Metformina en enfermedad renal diabética: estado actual

“…Por ejemplo, AMPK y autofagia con activación de rutas patológicas, tales como: las dianas de la rapamicina en mamíferos (mTOR), estrés del retículo endoplásmico, transición epitelio-mesénquima, estrés oxidativo e hipoxia (figura 2) 23 .…”