A Breath of Fresh Hope: Metformin Dry Powder Inhalation for Idiopathic Pulmonary Fibrosis Therapy

Idiopathic pulmonary fibrosis (IPF) represents a devastating, ultimately fatal lung disease that gradually transforms the intricate and vital alveolar network of the respiratory system into fibrotic scars without a clear and identifiable cause, making IPF a particularly challenging condition to manage and treat. Systemic administration of metformin has been reported to have a protective effect against IPF, thus, pulmonary administration of metformin raises the possibility of greater efficacy. This study evaluated the potential of metformin dry powder inhalation (DPI) in mitigating IPF and compared its efficacy with current treatment modalities. C57BL6J mice were used to build an IPF model using bleomycin. Hematoxylin-eosin (HE) and Masson staining were employed to observe pulmonary fibrosis. HPLC-MS/MS was used to examine the drug concentration in lung tissue. The results of this study indicate that Metformin DPI could improve lung injury induced by bleomycin. In addition, the effect of Metformin DPI was found to be much better than that of intraperitoneal injection. Most importantly, Metformin DPI was shown to be more efficient than nintedanib. In conclusion, our study is the first to demonstrate that Metformin DPI is capable of rescuing bleomycin-induced IPF in mice, offering a promising lead in exploring the therapeutic pathway of metformin inhalation for the treatment of pulmonary diseases.