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Metformin associated with increased risk for acute dialysis in type 2 diabetes
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Compared with sulfonylureas, metformin was associated with a 50% higher risk for acute dialysis in patients with type 2 diabetes, researchers in Denmark found.
“Treatment with metformin has been associated with acute kidney injury in vivo, and may be dose-dependently associated with acid-base imbalance and acute kidney injury,” Nicholas Carlson, MD, of the department of cardiology, Gentofte Hospital, Copenhagen University, and colleagues wrote. “However, conclusive evidence supporting an association with either lactic acidosis, acute kidney injury or acute dialysis continues to be insufficient.”
Carlson and colleagues performed a retrospective nationwide cohort study using patient records from Denmark’s public health care system (n = 168,443). All patients in the study had type 2 diabetes, were aged older than 50 years, and initiated treatment with either metformin or sulfonylurea in Denmark between 2000 and 2012. Most patients (70.7%, n = 119,153) began treatment with metformin, and 80.4% remained on their initial treatment for the duration of the study period.
At 1 year, 197 patients required acute dialysis, according to the researchers. Another 16 patients were diagnosed with end-stage renal disease, and 7,153 patients died. Cox regression analysis showed that compared with sulfonylurea, metformin was associated with an increased risk for acute dialysis (HR = 1.51; 95% CI, 1.06-2.17), and there was a decreased risk for death without dialysis (HR = 0.66; 95% CI, 0.62-0.70). The two treatments showed no difference in risk for end-stage renal disease (HR = 0.46; 95% CI, 0.18-1.20).
For patients using sulfonylurea, the absolute 1-year risk for acute dialysis was 92.4 per 100,000 (95% CI, 67.1-121.3), whereas for patients on metformin, the risk was 142.7 per 100,000 (95% CI, 118.3-168). The risk for acute dialysis was 50.3 per 100,000 higher for metformin compared with sulfonylurea, yielding an absolute risk ratio of 1.53 (95% CI, 1.06-2.23) and a number needed to harm of 1,988, according to researchers.
Women, older patients, those undergoing treatment at higher doses and patients with pre-existing renal insufficiency had a greater metformin-associated risk for acute dialysis. Carlson and colleagues wrote that metformin “could be altogether safe” in patients who were not of an advanced age and did not have compromised renal function.
“As guidelines governing management of type 2 diabetes increasingly advocate use of metformin as first-line treatment, our results underscore the clinical importance of discontinuation of metformin in cases of acute illness, particularly as continuance of treatment in patients with acute renal impairment could lead to metformin accumulation with induction of direct tubular damage and injury aggravation,” the researchers wrote. – by Andy Polhamus
Disclosure: Carlson reports no relevant financial disclosures. Please see the full study for a complete list of all other authors’ relevant financial disclosures.
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