Diabetes Treatment Using Metformin Is Associated with Protective Effect for Emphysema Progression in Smokers

Rationale: Type 2 Diabetes (T2D) is one of the leading chronic diseases among smokers. Chronic obstructive pulmonary disease (COPD) is common among people with diabetes, with the lung posited as an additional target organ of diabetes. Previous literature suggests that some medications treating comorbidities of COPD patients may also benefit lung function. Objectives: We used a novel statistical method to identify comorbidity medications associated with pulmonary function progression and assess potential effects using an adjusted mixed effect model among smokers with and without COPD. Methods: Participants from the COPDGene cohort who completed initial visit (P1) , and 5-year follow up (P2) from 20through 2017 with complete demographics, clinical information, and medication history were included in the study. A least absolute shrinkage and selection operator (LASSO) model with false discovery rate control by a knockoff filter was used to identify medication classes associated with COPD progression in participants with and without T2D treatment. An adjusted linear mixed model was then used to confirm the association between selected medication and the change in percent emphysema and other lung function variables from P1 to P2. Results: A total of 3,786 out of 10,198 smokers with complete information from P1 and P2 were included. Overall, 359 out of 3,786 smokers reported having T2D at P1, 2out of 359 patients were treated with the class of biguanides (metformin) at P1. The LASSO selection identified metformin as strongly associated with percent emphysema change. Adjusted linear mixed models confirmed that metformin use is associated with the reduction of emphysema in smokers (p<0.0001) from P1 to P2. Conclusions: Our study identified and confirmed an association between metformin and reduced emphysema progression among smokers with and without COPD. Metformin, a common treatment for diabetes, may also have protective effect on lung function. Disclosure Y.Li: Employee; Vertex Pharmaceuticals Incorporated. R.B.Conway: None. K.Young: None. K.A.Pratte: None. D.Foer: Research Support; IBM Watson Health. S.Rennard: Advisory Panel; GlaxoSmithKline plc., Sanofi, Verona, Verona, Consultant; Bergenbio, Boehringer Ingelheim International GmbH, NovoVentures. E.Austin: None. Y.Gwon: None. G.L.Kinney: None. Funding U01HL089897U01HL089856