Metformin May Be of Benefit, Even in Advancing Kidney Disease

Nancy A. Melville

April 02, 2020

The use of metformin among people with type 2 diabetes who have chronic kidney disease (CKD) is associated with a reduced risk of death and end-stage renal disease (ESRD) — without increasing the risk of lactic acidosis — a new observational study from South Korea shows.

"In patients with advanced CKD, if metformin is used carefully while monitoring, it could be suggested as a treatment [for type 2 diabetes] that can slow the progress of kidney disease as well as [having a] cardiovascular benefit," lead author Jung Pyo Lee, MD, PhD, of Seoul National University Boramae Medical Center, told Medscape Medical News.

In recent years, guidance from the US Food and Drug Administration has recommended relaxation of metformin use in patients with type 2 diabetes and CKD, but only for those with less severe renal disease. Concerns about its use center on the perceived risk of lactic acidosis with the agent.

So for those with moderate CKD stage 3B disease (estimated glomerular filtration rate [eGFR] 30 to < 45 mL/min/1.73m2), metformin use still "remains controversial," say the Korean researchers, led by Soie Kwon, of Seoul National University Hospital, writing in Diabetes Care.

And avoidance of metformin is still advised for those with very poor kidney function (eGFR < 30 mL/min/1.73m2).

Now these new results "support a recent trend that metformin can be considered in CKD 3B patients 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," Kwon and colleagues note.

Asked to comment, Samira Bell, MB, a consultant nephrologist, Renal Unit, Ninewells Hospital, Dundee, UK, agreed: "There is increasing evidence that treatment with metformin in patients with mild to moderate CKD is safe and may also confer a survival benefit."

"However, randomized controlled trial evidence is required before widespread use of metformin in patients with eGFR < 30 mL/min/1.73m2 can be recommended," she emphasized.

"Very Low" Rate of Lactic Acidosis, Even in Stage 4 CKD, Is Reassuring

Kwon and colleagues report on 10,426 patients with type 2 diabetic kidney disease from two hospitals in South Korea.

Overall, 13.8% of patients treated with metformin died during a median follow-up of 7.3 years and 11.4% progressed to ESRD, defined as needing dialysis for longer than 3 months or renal transplantation. Of those who did not receive metformin, 26.8% died and 24.5% progressed to ESRD.

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, seen after approximately 2.5 years of metformin use.

The reduction in mortality risk remained significant regardless of kidney function.

Relative to nonusers in the same categories, metformin users with eGFR ≥ 45 mL/min/1.73m2 had a 30% reduced risk, and those in the middle (30 to < 45 mL/min/1.73m2) and lowest (< 30 mL/min/1.73m2) 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/1.73m2 but not among those with the poorest kidney function (< 30 mL/min/1.73m2).

The researchers note that only one individual in their study experienced a lactic acidosis event thought to be linked to metformin, and people taking metformin did not have a significantly higher risk for all-cause lactic acidosis than those taking other diabetes drugs.

Katherine R. Tuttle, MD, professor of medicine at the University of Washington, Seattle, said: "The findings are reassuring that the risk of lactic acidosis is very low even in stage 4 CKD [eGFR < 30 mL/min/1.73m2]."

Metformin may be a valuable agent for preventing the major complications of CKD — death and kidney failure — among patients with type 2 diabetes and low eGFR.

However, the results must be interpreted with caution given their retrospective and observational nature, she cautioned.

Kwon and colleagues concur, concluding: "Well-organized randomized controlled trials are necessary" to confirm the findings.

The study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare, Republic of Korea. The authors, Tuttle, and Bell have reported no relevant financial relationships.

Diabetes Care. Published online March 4, 2020. Abstract

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