Metformin Raises Acidosis Risk in Some With Poor Renal Function
Among patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) of less than 30 ml/min/1.73 m2, metformin use is associated with an increased risk for lactic acidosis.1
Researchers made this determination based on the results of a study of 75,413 patients (primary cohort) with diabetes in the Geisinger Health System. All participants had received a time-dependent assessment of eGFR stage between January 2004 and January 2017. Median follow-up lasted 5.7 years.
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Subsequently, the results were replicated in 67,758 new users of metformin and 14,439 new users of sulfonylurea from 2010 to 2015 (replication cohort). Data were obtained from 350 US private health systems. The primary outcome was hospitalization due to acidosis.
A total of 2335 hospitalizations due to acidosis occurred over the course of follow-up. Results of the study indicated that time-dependent metformin use was not associated with incident acidosis overall (adjusted hazard ratio [HR] 0.98), in patients with an eGFR of 45 to 59 mL/min/1.73 m2 (adjusted HR 1.16) or an eGFR of 30 to 44 mL/min/1.73 m2 (adjusted HR 1.09) compared with alternative forms of diabetes management.
However, metformin use was found to be associated with an elevated risk for acidosis among patients with an eGFR of less than 30 mL/min/1.73 m2 (adjusted HR 2.07).
The researchers noted that these findings remained consistent when comparing new metformin users with new sulfonylurea users (adjusted HR for eGFR 30 to 44 mL/min/1.73 m2: 0.77), when excluding baseline insulin users (adjusted HR for eGFR 30 to 44 mL/min/1.73 m2: 1.16), and in the replication cohort (adjusted HR for eGFR 30-44 mL/min/1.73 m2: 0.86).
“In 2 real-world clinical settings, metformin use was associated with acidosis only at eGFR less than 30 mL/min/1.73 m2,” the researchers concluded. “Our results support cautious use of metformin in patients with type 2 diabetes and eGFR of at least 30 mL/min/1.73 m2.”
—Christina Vogt
Reference:
1. Lazarus B, Wu A, Shin JI, et al. Association of metformin use with risk of lactic acidosis across the range of kidney function: a community-based cohort study. JAMA Intern Med. 2018;178(7):903-910. doi:10.1001/jamainternmed.2018.0292