Supplementary Material for: Metformin Does Not Affect Clinically Relevant Outcomes in Patients with Idiopathic Pulmonary Fibrosis P.Spagnolo M.Kreuter T.M.Maher W.Wuyts F.Bonella T.J.Corte S.Kopf D.Weycker K.-U.Kirchgaessler C.J.Ryerson 2018 <b><i>Background:</i></b> Diabetes mellitus is a possible risk factor for the development of idiopathic pulmonary fibrosis (IPF), yet the effect of antidiabetic therapy on the course of IPF is unknown. <b><i>Objectives:</i></b> This post hoc analysis assessed the effect of metformin on clinically relevant outcomes in patients with IPF. <b><i>Methods:</i></b> For the primary analysis, patients randomized to placebo (<i>n</i> = 624) in 3 phase 3, double-blind, controlled trials of pirfenidone (CAPACITY [NCT00287716 and NCT00287729]; ASCEND [NCT01366209]) were categorized by baseline metformin use. The primary outcome was disease progression (forced vital capacity [FVC] decline ≥10%, 6-min walking distance [6MWD] decline ≥50 m, or death). Other outcomes included mortality, hospitalization, FVC decline (≥10 and ≥5%), and 6MWD decline. Outcomes were also assessed in patients with diabetes and/or hyperglycemia (impaired glucose tolerance [IGT] and diabetes population [IGT-diabetes population]) and all patients included in the 3 studies (intention-to-treat [ITT] population). <b><i>Results:</i></b> Overall, 71 (11.4%) patients were metformin users and 553 (88.6%) were nonmetformin users. Baseline data were similar between groups, except for a higher percentage of males (84.5 vs. 73.2%) and a history of diabetes (98.6 vs. 11.6%) in metformin users versus nonmetformin users. The unadjusted 1-year analyses demonstrated no significant differences in disease progression or other outcomes. A higher proportion of metformin users compared with nonmetformin users had a relative FVC decline of ≥5% (63.4 vs. 50.6%, <i>p</i> = 0.043). Results were similar for the IGT-diabetes population and for the ITT population. Multivariable analyses yielded similar results. <b><i>Conclusions:</i></b> Metformin has no effect on clinically relevant outcomes in patients with IPF.