Source: Inzucchi SE, et al. Metformin in patients with type 2 diabetes and kidney disease: A systematic review. JAMA 2014;312:2668-2675.

Boundaries devised by regulatory agencies around the world for safe use of metformin differ from FDA labelling in the United States; many other nations allow more liberal use of metformin, indicating it is safe at lower levels of renal function than the boundaries you and I are used to: creatinine ≥ 1.5 md/dL for men, ≥ 1.4 mg/dL for women, or an eGFR < 60 mL/min/1.73 m2. The observation that metformin has been used in patients with chronic kidney disease (CKD) beyond these boundaries safely, and the relative rarity of lactic acidosis related to metformin in the United States, have stimulated a reappraisal of the recommendations for patients with CKD. Metformin is cleared by the kidneys, but the original dosing and safety recommendations put into place more than 20 years ago are reportedly based on potential administration of metformin at doses up to 3 g/d, which of course is substantially above the usual maximum dose actually used in the United States (2000-2550 mg/d).

Inzucchi et al reviewed the literature in reference to studies that evaluated metformin, kidney disease, and lactic acidosis. Several trials even included plasma metformin measured at eGFR levels as low as < 30 mL/min. The authors opine that — contingent on regular monitoring — metformin might be safely used in diabetics with CKD down to an eGFR as low as 30 mL/min.