Metformin use in renal dysfunction: Is a serum creatinine threshold appropriate?

• Published in: American journal of health-system pharmacy Vol. 66; no. 22; pp. 2017 - 2022
• Main Authors: Philbrick, Ann M, Ernst, Michael E, McDanel, Deanna L, Ross, Mary B, Moores, Kevin G
• Format: Journal Article
• Language: English
• Published: England American Society of Health-System Pharmacists 15-11-2009; Oxford University Press
• Subjects: Acidosis, Lactic - chemically induced; Care and treatment; Complications and side effects; Creatinine; Creatinine - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diagnosis; Health aspects; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Kidney diseases; Kidney Diseases - complications; Kidney Diseases - physiopathology; Lactic Acid - blood; Metformin; Metformin - adverse effects; Metformin - therapeutic use; Physiological aspects; Risk Factors; United States
• ISSN: 1079-2082; 1535-2900
• DOI: 10.2146/ajhp080330

The relationship among metformin use, plasma lactate levels, and lactic acidosis in patients with type 2 diabetes mellitus and the appropriateness of metformin use in patients with renal dysfunction are discussed.
A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes recommends metformin therapy as first-line therapy along with lifestyle modification to treat type 2 diabetes mellitus. Despite this recommendation, metformin may be underutilized due to the fear of metformin-associated lactic acidosis and because its use is contraindicated in patients with renal dysfunction. Several studies have attempted to characterize the relationship among plasma metformin levels, plasma lactate levels, and lactic acidosis. However, a causal relationship between metformin and lactic acidosis has not been definitively established. In the United States, the estimated rate of lactic acidosis among diabetic patients treated with metformin is similar to that of diabetic patients not taking metformin. Despite specific guidelines advising against prescribing metformin in renal dysfunction, published reports indicate that metformin is continued in 25% of patients after the contraindication is discovered. Individual studies point to a possible correlation between metformin levels and plasma lactate levels, but mortality does not appear to correlate with plasma metformin levels. These results indicate that there may not be a direct relationship between plasma lactate and metformin levels.
Current studies point to a weak causal relationship between metformin and lactic acidosis. In patients without comorbid conditions that would predispose them to lactic acidosis, elevated serum creatinine levels should be considered a risk factor for the development of lactic acidosis but not an absolute contraindication.