Metformin does not increase the risk for lactic acidosis in patients with type 2 diabetes who have estimated glomerular filtration rate (eGFR) as low as 30 mL/min/1.73 m2, according to new study findings published online in JAMA Internal Medicine.

Currently, the FDA recommends against starting metformin in patients with an eGFR of 30 to 45 mL/min/1.73 m2.

Morgan E. Grams, MD, PhD, of Johns Hopkins University in Baltimore, and colleagues determined that metformin was associated with acidosis only at eGFR less than 30 mL/min/1.73 m2 in analyses of 2 large databases including more than 115,000 patients. Study results support the FDA’s contraindication against using metformin in patients with an eGFR below 30 mL/minute/1.73 m2.

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The drug presented no greater risk of acidosis at higher eGFRs, compared with alternative diabetes medications, such as sulfonylureas. Unlike previous studies, the investigators accounted for individual variation in eGFR over time and for confounding by insulin use. They also adjusted results for demographics, cardiovascular risk factors, HbA1c, and other medications.

“These findings support the recent expansion of the eGFR thresholds for metformin use by the FDA, and recommendations from other regulatory bodies, which suggest that metformin can be used when eGFR is 45 to 59 mL/min/1.73 m2 and cautiously when eGFR is 30 to 44 mL/min/1.73m2”, Dr Grams and his team wrote.

In an accompanying editorial, Chester B. Good, MD, MPH, of the Pittsburgh VA Medical Center, and Leonard M. Pogach, MD, MBA, of the Department of Veterans Affairs New Jersey Healthcare System in East Orange, added some caveats. “At a minimum, patients in this category should have a repeated eGFR measurement given the limitation in the accuracy of a single eGFR determination. If receiving metformin, those at higher risk for dehydration due to concomitant medication use (especially sodium-glucose co-transporter 2 inhibitors and diuretics), social circumstances, and comorbid conditions should be carefully monitored for symptoms or worsening renal function.”

They urged shared decision-making since the pros and cons of metformin have not been directly and sufficiently compared with newer agents.

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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. doi:10.1001/jamainternmed.2018.0292.

Good CB and Pogach LM. Should metformin be first-line therapy for patients with type 2 diabetes and chronic kidney disease? Informed patients should decide. JAMA Intern Med. doi:10.1001/jamainternmed.2018.0301

FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function. FDA; April 2017.