A new study suggests that metformin, a drug widely used to treat diabetes, can benefit people with idiopathic pulmonary fibrosis (IPF) by working to diminish lung fibrosis.
The study, “Metformin Attenuates Lung Fibrosis Development Via NOX4 Suppression,” was published in the journal Respiratory Research by Nahoko Sato, MD, and colleagues from different research institutions in Japan. The study sheds light into the mechanisms of action of metformin.
In IPF, certain components of the inflammatory response, such as cytokine TGF-β, can regulate how myofibroblasts (cells important for wound healing and organ remodeling) accumulate in the lungs, thereby controlling the development of lung fibrosis. In turn, the activity of TGF-β is regulated by the presence of reactive oxygen species (ROS), toxic compounds that derive from the process of energy production in cells.
One of the main contributors to ROS production is the protein NOX4, whose levels are known to be higher than usual in the lungs of IPF patients, suggesting this protein — and ROS accumulation — play a role in the chain of events that lead to the development of lung fibrosis.
Researchers tested whether reducing the levels of NOX4 would lead to a decrease in the production of ROS and in the activation of TGF-β and, consequently, diminish lung fibrosis.
To do so, they analyzed the inhibitory effect of metformin, a medication used by type 2 diabetics to lower blood glucose levels, and which has shown an ability to work as an anti-fibrotic against the formation of myofibroblasts induced by TGF-β in the lung.
The team observed that, indeed, cultures of lung cells treated with metformin presented lower levels of NOX4 and ROS, which were associated with less activation of TGF-β and less production of myofibroblasts.
Moreover, mice models of lung fibrosis treated with metformin had a significant reduction of the development of the disease. The authors also observed that the lungs of these animals presented a clear reduction in NOX4 levels.
“In summary, we elucidated that metformin … attenuates lung fibrosis development by inhibiting TGF-β signaling through NOX4 suppression,” the authors wrote. “We consider metformin to be a promising candidate agent for an antifibrotic modality of treatment for IPF patients.”
They concluded that metformin showed promise as a treatment for IPF, and noted that this already approved drug has proven efficacy and safety.
“The advantages of drug repositioning are decreased risks for unexpected adverse effects and simplified clinical trials,” the authors wrote. “Metformin is widely used for type II diabetes patients in clinical settings with acceptable adverse events.”
Future studies are now required to confirm the possible use of metformin as an anti-fibrotic agent in the treatment of IPF.
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