Metformin Use in Type 2 Diabetic Chronic Kidney Disease Patients May Increase Mortality Risk

Metformin Use in Type 2 Diabetic Chronic Kidney Disease Patients May Increase Mortality Risk

Metformin, a first-line treatment for type 2 diabetes, may not be appropriate in certain patients with chronic kidney disease. Researchers at Taipei Veterans General Hospital assessed metformin use in type 2 diabetes patients with stage 5 chronic kidney disease and found an increase in all-cause mortality.

“Use of metformin in people with type 2 diabetes and a serum creatinine concentration greater than 530 μmol/L is associated with a significantly increased risk of all-cause mortality compared with non-users,” wrote Szu-Chun Hung, MD, lead author on the research team’s paper, “Metformin Use and Mortality in Patients With Advanced Chronic Kidney Disease: National, Retrospective, Observational, Cohort Study,” which was published in The Lancet Diabetes & Endocrinology. According to Dr. Hung, “Metformin use should not be encouraged in this patient group.”

The researchers were interested in conducting a study into metformin use in patients with chronic kidney disease, as previous reports have suggested the risk of lactic acidosis as a result of metformin use in patients with impaired kidney function. Individuals with mild-to-moderate chronic kidney disease may also be cautious to use metformin, but the team was specifically interested in type 2 diabetics with stage 5 chronic kidney disease.

Over 1,000 type 2 diabetic chronic kidney disease patients were treated with metformin in the retrospective study period, and were compared to 11,345 non-users. The research team used all-cause mortality as an outcome for the safety of metformin treatment. In the end, 813 metformin users and 2439 non-users were compared.

Although the groups were not significantly different in baseline characteristics of clinical and socioeconomic variables, they were different in terms of all-cause mortality. Metformin use independently predicted all-cause mortality, as 53% of users were affected, compared to 41% of non-users.

One possible explanation could be metabolic acidosis, but there was only a higher (not significant) risk for metabolic acidosis in metformin users compared to non-users. However, a review article written last year, “Metformin in Patients With Type 2 Diabetes and Kidney Disease: A Systematic Review,” which was published in The Journal of the American Medical Association, suggested that lactic acidosis may not be the reason why metformin can be hazardous in chronic kidney disease patients with type 2 diabetes. “The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100,000 person-years to 10 per 100,000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes,” stated the authors. Therefore, to determine the cause for increased mortality in chronic kidney disease patients with type 2 diabetes, a larger prospective trial may be required.

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Maureen Newman currently works as a PhD student studying biomedical engineering at University of Rochester, working towards a career of research in biomaterials for drug delivery and regenerative medicine. She is an integral part of Dr. Danielle Benoit’s laboratory, where she is investigating bone-homing therapeutics for osteoporosis treatment.

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