Metformin protects renal tubular cells; mechanisms and new concepts

Context: The prevalence of diabetes markedly increased in recent decades. It is well accepted that the risk of morbidity and fatality increases in patients with type 2 diabetes (T2DM).
Evidence Acquisition: An electronic search was performed to detect suitable studies, with keywords of metformin, prediabetes, diabetes Mellitus, Gentamicin and lactic acidosis.
Metformin (biguanide) is widely used as the first pharmacological option in pre-diabetic subjects and patients with T2DM. Low-cost, long-term effect, low risk of hypoglycemia, and ease in utilization are considered as significant benefits of metformin compared with other therapies. Numerous studies have explored that medicinal intervention particularly metformin administration not only can decrease high blood glucose in patients with T2DM but also can avoid or postpone the beginning of clinical T2DM in pre-diabetic cases. Protective effect of metformin on renal cells by different mechanisms is described here. Gentamicin is an important factor that affects kidney function and structure. Nephrotoxicity is one of the serious side effects of gentamicin (an aminoglycoside antibiotic). Numerous investigation showed the protective effect of metformin against the gentamicin nephrotoxicity. On the other hand, lactic acidosis is known as an uncommon but serious side effect of metformin that should be mentioned. Signs of lactic acidosis are defined by plasma lactate levels higher than 5 mmol/L and pH smaller than 7.4.
Different small series and large experimental investigations have discovered the association between metformin and lactic acidosis summarized here.