Apart from its glucose-lowering actions, metformin is likely to display reno protective effects in patients with type 2 diabetes and chronic kidney disease. However, its use in patients with chronic kidney disease has been a controversial subject for many years, majorly due to the associated risk of lactic acidosis. To support the positive role of metformin, a recent study showed that it appears to be safe and pharmacologically effective in patients with moderate-to-severe chronic kidney disease, when the dose is adjusted for the degree of renal failure. Various organizations have put forward different recommendations on the use of metformin in this patient population. The joint position statement of the American Diabetes Association and European Association for the Study of Diabetes suggests that it is reasonable to use metformin down to a glomerular filtration rate (GFR) of 30 mL/min/1.73 m², with further dose reduction at a GFR of 45 mL/min/1.73 m². In such cases, it is advisable to monitor GFR frequently, and the drug should be discontinued if the clinical situation worsens or if dehydration and hypoxemia occurs. Besides, the European Medicines Agency and the advisory board of European Renal Best Practice have also indicated the use of metformin in patients with a GFR as low as 30 mL/min/1.73 m², with dose alterations based on renal function. In Australia, while metformin is contraindicated if GFR is < 30 mL/min/1.73 m², it can be used cautiously in those with a GFR of 30–45 mL/min/1.73 m² according to the National Evidence-Based Guidelines for blood glucose control in type 2 diabetes mellitus.

Furthermore, type 2 diabetes mellitus may also enhance the risk of fragility fractures, mostly due to a combination of factors, including a greater risk of falling, regional osteopenia, and impaired bone quality. Lower bone quality in diabetic patients is mainly due to hyperglycemia, toxic effects of advanced glycosylation end-products (AGEs) on bone tissue, and impaired bone microvascular system. AGEs may also underline the development of osteoarthritis and further osteoporosis. Despite being two different clinical conditions, diabetes mellitus and osteoporosis are likely to occur together. Therefore, it is essential to attain optimal glycemic control while minimizing the risk of hypoglycemia and avoiding medications with a proven negative effect on bone metabolism.With regard to this, metformin seems to be a beneficial drug. It exhibits osteogenic effects and mayprotect against fragility fractures. Moreover, the researchers have demonstrated that metformin intake can prevent deterioration of bone microarchitecture caused by insulin deficiency.

Therefore, metformin could have a unique place in the arsenal of oral hypoglycemic drugs for diabetic patients with chronic kidney disease or those with diabetes-related osteoporosis.

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