Paolo Spagnolo1, Michael Kreuter2, Toby M Maher3,4, Wim Wuyts5, Francesco Bonella6, Tamera J Corte7, Stefan Kopf8, Derek Weycker9, Klaus-Uwe Kirchgaessler10, Christopher J Ryerson11. 1. Section of Respiratory Diseases, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy. 2. Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Critical Care Medicine, Thoraxklinik, University of Heidelberg, Member of the German Center for Lung Research, Heidelberg, Germany. 3. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, United Kingdom. 4. Fibrosis Research Group, National Heart and Lung Institute, Imperial College London, London, United Kingdom. 5. Department of Respiratory Medicine, University Hospitals Leuven, Leuven, Belgium. 6. Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany. 7. Department of Respiratory Medicine, Royal Prince Alfred Hospital and University of Sydney, Sydney, New South Wales, Australia. 8. Department of Endocrinology, Metabolism and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany. 9. Policy Analysis Inc. (PAI), Brookline, Massachusetts, USA. 10. F. Hoffmann-La Roche, Ltd., Basel, Switzerland. 11. Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Abstract
BACKGROUND: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. OBJECTIVES: This post hoc analysis assessed the effect of metformin on clinically relevant outcomes in patients with IPF. METHODS: For the primary analysis, patients randomized to placebo (n = 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). RESULTS: 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%, p = 0.043). Results were similar for the IGT-diabetes population and for the ITT population. Multivariable analyses yielded similar results. CONCLUSIONS:Metformin has no effect on clinically relevant outcomes in patients with IPF.
RCT Entities:
BACKGROUND: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. OBJECTIVES: This post hoc analysis assessed the effect of metformin on clinically relevant outcomes in patients with IPF. METHODS: For the primary analysis, patients randomized to placebo (n = 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). RESULTS: 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%, p = 0.043). Results were similar for the IGT-diabetes population and for the ITT population. Multivariable analyses yielded similar results. CONCLUSIONS:Metformin has no effect on clinically relevant outcomes in patients with IPF.
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