Association of metformin with lung function decline and mortality in fibrotic interstitial lung disease: an observational cohort study

Many patients with fibrotic interstitial lung disease (ILD) also have comorbid diabetes, for which they take metformin. Metformin use has been shown to have lung fibrosis attenuation potential based on laboratory research but studies in human populations have yielded inconsistent results. To investigate this, 2,226 patients with fibrotic ILD from the large, prospective Canadian Registry for Pulmonary Fibrosis were analyzed for lung function at baseline and up to 2-year follow up. Joint modeling was used to assess the association of baseline metformin use with longitudinal lung forced vital capacity change and survival (death or lung transplant), adjusting for age, sex, smoking pack-years, baseline lung function, medication use. Results showed that baseline metformin use was not significantly associated with attenuation of forced vital capacity decline in the overall interstitial lung disease cohort, or in the subgroups based on presence of a diagnosis of idiopathic pulmonary fibrosis or diabetes. Kaplan–Meier and Cox analyses suggested a trend toward increased mortality or transplant risk associated with metformin use in all cohorts, although this was not statistically significant after adjustment for other variables. In our study, metformin did not significantly alter lung function decline in fibrotic ILD despite laboratory evidence of antifibrotic properties.