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Metformin may reduce mortality in patients with certain chronic diseases

Recent changes in metformin labeling by the FDA is supported by new findings published in Annals of Internal Medicine that suggest that patients with chronic kidney disease, congestive heart failure and chronic liver disease receiving the drug experienced improvements in all-cause mortality.

“Recent changes to the U.S. [FDA] boxed warning for metformin will increase its use in persons with historical contraindications or precautions,” Matthew J. Crowley, MD, MHS, of the Durham Veterans Affairs Medical Center, and colleagues wrote. “Prescribers must understand the clinical outcomes of metformin use in these populations.”

Crowley and colleagues searched several databases from January 1994 to September 2016 to quantitatively and qualitatively synthesize data and evaluate outcomes of metformin use in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (estimated glomerular filtration rate less than 60 mL/min/1.73 m²), congestive heart failure or chronic liver disease with hepatic impairment.

Seventeen observational studies were included in the analysis. Results indicated that metformin treatment was associated with a reduction in all-cause mortality for all three chronic diseases that were analyzed. A reduction in heart failure readmissions in patients with chronic kidney disease or congestive heart failure was also associated with metformin use. However, the researchers note that these findings were based on limited evidence.

“Available data provide no evidence that the risks associated with metformin exceed those of other antihyperglycemic medications in these populations,” Crowley and colleagues concluded. “Our findings support the recent FDA labeling changes, point toward areas for future research, and may help inform clinical practice and revision of clinical guidelines.”

In a related editorial, Kasia J. Lipska, MD, MHS, from Yale School of Medicine, argued that since the review contained several limitations, such as using only observational studies that did not contain blinded outcomes assessments, the benefits of treating patients with kidney, heart or liver dysfunction with metformin remains unclear.

“The resulting imbalance in the available evidence may potentially lead to greater use of newer medications, in lieu of metformin, and cost an already taxed health care system billions of dollars,” she concluded. “In light of the recently relaxed contraindications for its use, bolstering the evidence base for metformin might be a wise investment.” – by Alaina Tedesco

Disclosure: Crowley and colleagues report primary funding from the U.S. Department of Veterans Affairs. Lipska reports receiving support from the National Institute on Aging, the American Federation of Aging Research and the Claude D. Pepper Older Americans Independence Center.