medwireNews: Observational study results suggest that metformin use is associated with a reduced risk for mortality and progression to end-stage renal disease (ESRD), and does not increase the risk for lactic acidosis, among people with type 2 diabetes and chronic kidney disease (CKD).
Currently, metformin “is not recommended in individuals with impaired kidney function because of the perceived risk of lactic acidosis,” say the researchers. They note that the US FDA restricts use of the drug in people with an estimated glomerular filtration rate (eGFR) of less than 30 mL/min per 1.73 m2, while its use in those with an eGFR of 30–45 mL/min per 1.73 m2 “is controversial.”
Jung Pyo Lee (Seoul National University Boramae Medical Center, South Korea) and study co-authors used electronic medical records to evaluate adverse outcomes among 10,862 individuals with type 2 diabetes treated at two nephrology clinics in Seoul between 2001 and 2016.
In all, 13.8% of 4597 patients treated with metformin died over a median follow-up of 7.3 years, compared with 26.8% of the 6265 who did not receive metformin, while 11.4% and 24.5%, respectively, progressed to ESRD, defined as needing dialysis for longer than 3 months or renal transplantation.
After propensity score matching to account for differences in baseline characteristics between the two groups, 2704 metformin users had a significant 35% lower risk for all-cause mortality and a significant 33% lower risk for ESRD progression than the same number of nonusers. These associations were seen after approximately 2.5 years of metformin use.
Lee and team report that this reduction in mortality risk remained significant regardless of kidney function. Relative to nonusers in the same categories, metformin users with the highest eGFR (≥45 mL/min per 1.73 m2) had a 30% reduced risk, while those in the middle (30 to <45 mL/min per 1.73 m2) and lowest (<30 mL/min per 1.73 m2) groups had a 36% and 45% reduced risk, respectively.
Additionally, the association between metformin and a lower risk for progression to ESRD was significant among patients with an eGFR of at least 30 mL/min per 1.73 m2, but not among those with the poorest kidney function.
The researchers note that only one individual in their study experienced a lactic acidosis event thought to be linked to metformin, and people using metformin did not have a significantly higher risk for all-cause lactic acidosis than those taking other diabetes drugs.
These results “support a recent trend that metformin can be considered in CKD 3B patients [eGFR 30 to <45 mL/min per 1.73 m2] because of its association with decreasing all-cause mortality and delaying ESRD progression and because of its association with a low incidence of lactic acidosis,” write Lee et al in Diabetes Care.
They caution, however, that “well-organized randomized controlled trials are necessary” to confirm their findings.
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