Duke Health Referring Physicians


Metformin May Be Effective in Previous Contraindications

A recent review of current outcome data regarding metformin, a first-line drug for type 2 diabetes mellitus in the United States since the mid-1990s, has prompted new assessment of the drug’s association with reduced mortality rates in patients with chronic kidney disease (CKD), congestive heart failure (CHF), and chronic liver disease (CLD).

Concerns about lactic acidosis have limited the use of metformin in patients with CKD, CHF, and CLD. But, a safety announcement from the US Food and Drug Administration (FDA) in April 2016 allowed it to be used to treat certain patients with reduced kidney function.

The review, published in the February 2017 issue of Annals of Internal Medicine, supported the FDA’s decision and encouraged additional clinical trials to examine the effectiveness of the drug in the setting of previously contraindicated conditions. The review was supported by the US Veterans Affairs Administration in conjunction with the Durham Center for Health Services Research and Development in Primary Care.

The systematic review examined existing studies, all-cause mortality, and major cardiovascular events in patients with CKD (estimated glomerular filtration rate < 60 mL/minute/1.73 m2), CHF, or CLD with hepatic impairment.

Lead author Matthew J. Crowley, MD, a Duke endocrinologist and researcher, says the findings indicate metformin use may be associated with lower rates of mortality in patients with mild to moderate CKD, CHF, and CLD.

“This is an important topic for clinical practice because metformin has traditionally been withheld from patients with these conditions, and recent FDA changes may not be widely recognized,” Crowley says. “There’s justification now for using metformin more broadly.”

Crowley and other researchers from the Durham VA Evidence-based Synthesis Program concluded that metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key clinical outcomes.

A key recommendation of the meta-analysis and review, however, was the need for additional randomized clinical trials. But Crowley warns that the widespread use of the drug presents challenges for researchers.

“The time and cost required to assess long-term outcomes such as mortality may be a barrier to randomized trials of a generic medication in such common use,” he says. The researchers concluded that observational studies may be a valuable alternative data source, because metformin use will likely increase in populations where historical precautions have been in place.

“The key message is that metformin is an affordable and well-tolerated drug that appears to benefit a lot of people who historically have not been eligible to use it,” Crowley says. “There is increasing support for broader use in the medical community.”

In addition to Crowley, other researchers were associated with Duke Health or the Durham VA Evidence-based Synthesis Program. They include Clarissa J. Diamantidis, MD, Jennifer R. McDuffie, PhD, C. Blake Cameron, MD, John W. Stanifer, MD, Clare K. Mock, MD, Xianwei Wang, MD, Shuang Tang, PhD, Avishek Nagi, MS, Andrzej S. Kosinski, PhD, and John W. Williams Jr, MD.