Metformin Linked With Increased Mortality In Diabetic Kidney Disease Patients

Prof. Der-Cherng Tarng, MD, PhD Division of Nephrology Taipei Veterans General Hospital, and National Yang-Ming University, Taiwan

Prof. Der-Cherng Tarng Interview with:
Prof. Der-Cherng Tarng, MD, PhD
Division of Nephrology
Taipei Veterans General Hospital, and
National Yang-Ming University, Taiwan

MedicalResearch: What is the background for this study? What are the main findings?

Prof. Tarng: Metformin is generally recommended as a first-line therapy for type 2 diabetes mellitus, but the use of metformin has been limited in patients with impaired kidney function because of the perceived risk of lactic acidosis. More recently, available evidence supports the cautious expansion of metformin use in patients with mild to moderate chronic kidney disease (CKD). However, no studies have yet examined whether metformin can be prescribed more widely to patients with advanced CKD.

We conducted a propensity score-matched cohort study using Taiwan’s National Health Insurance Research Database to assess the safety of metformin in patients with type 2 diabetes and serum creatinine levels >6 mg/dL, enrolled between January 1, 2000 and June 30, 2009 and followed-up until December 31, 2009, before Taiwan’s prescribing guidelines for metformin contraindicated its use in patients with CKD. From a consecutive sample of 12350 patients, 1005 (8.1%) were metformin users. Of these, 813 were successfully matched 1:3 to 2439 metformin nonusers. After multivariate adjustment, metformin use remained was an independent risk factor for mortality (hazard ratio 1.35, 95% confidence interval 1.20–1.45; p<0.0001). The increased risk was dose-dependent and was consistent across all subgroup analyses. However, metformin users compared with non-users were associated with a higher but insignificant risk of metabolic acidosis (hazard ratio 1.30, 95% confidence interval 0.88–1.93; p=0.188).

MedicalResearch: What should clinicians and patients take away from your report?

Prof. Tarng: There is no firm link between metformin and lactic acidosis, even in diabetic patients with advanced CKD. However, metformin use is associated with an increased risk of death in this patient population. The clinical benefits of metformin for diabetic patients with normal renal function should not extend to patients with advanced CKD. Someone who was once a friend can become an enemy!

MedicalResearch: What recommendations do you have for future research as a result of this study?

Prof. Tarng: Further study is required to understand the exact mechanisms of increased death risk associated with metformin use in diabetic patients with advanced CKD. Although randomised controlled studies are required to confirm or refute our findings, it may not be feasible to perform clinical trials to test the safety of metformin in these patients. Hence, high quality observational data may be the highest level of evidence that will ever be available regarding this condition.


Metformin use and mortality in patients with advanced chronic kidney disease: national, retrospective, observational, cohort study

Szu-Chun Hung, MD, Yu-Kang Chang, PhD, Jia-Sin Liu, MS, Ko-Lin Kuo, MD, Yu-Hsin Chen, MD Prof Chih-Cheng Hsu, MD,Prof Der-Cherng Tarng, MD

The Lancet Published Online: 17 June 2015
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Prof. Der-Cherng Tarng, MD, Ph (2015). Metformin Linked With Increased Mortality In Diabetic Kidney Disease Patients 

Last Updated on August 12, 2015 by Marie Benz MD FAAD