Skip to main content
eScholarship
Open Access Publications from the University of California

Risks of Metformin in Type 2 Diabetes and Chronic Kidney Disease: Lessons Learned from Taiwanese Data.

  • Author(s): Rhee, Connie M
  • Kovesdy, Csaba P
  • Kalantar-Zadeh, Kamyar
  • et al.

Published Web Location

https://doi.org/10.1159/000450862Creative Commons 'BY' version 4.0 license
Abstract

Like other biguanide agents, metformin is an anti-hyperglycemic agent with lower tendency towards hypoglycemia compared to other anti-diabetic drugs. Given its favorable effects on serum lipids, obese body habitus, cardiovascular disease, and mortality, metformin is recommended as the first-line pharmacologic agent for type 2 diabetes in the absence of contraindications. However, as metformin accumulation may lead to type B non-hypoxemic lactic acidosis, especially in the setting of kidney injury, chronic kidney disease, and overdose, regulatory agencies such as the United States Food and Drug Administration (FDA) have maintained certain restrictions regarding its use in kidney dysfunction. Case series have demonstrated a high fatality rate with metformin-associated lactic acidosis (MALA), and the real-life incidence of MALA may be underestimated by observational studies and clinical trials that have excluded patients with moderate-to-advanced kidney dysfunction. A recent study of advanced diabetic kidney disease patients in Taiwan in Lancet Endocrinology and Diabetes has provided unique insight into the potential consequences of unrestricted metformin use, including a 35% higher adjusted mortality risk that was dose-dependent. This timely study, as well as historical data documenting the toxicities of other biguanides, phenformin and buformin, suggest that the recent relaxation of FDA recommendations to expand metformin use in patients with kidney dysfunction (i.e., those with estimated glomerular filtration rates ≥30 instead of our recommended ≥45 ml/min/1.73 m2) may be too liberal. In this article, we will review the history of metformin use; its pharmacology, mechanism of action, and potential toxicities; and policy-level changes in its use over time.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View