Metformin does not affect clinically relevant outcomes in patients with idiopathic pulmonary fibrosis
Open accessAbstract
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Post-hoc analysis of metformin versus non-metformin in the placebo arms of three IPF trials revealed that metformin had no significant effect on disease progression, lung function decline, and mortality in IPF.
“a post-hoc analysis of metformin versus non-metformin in the placebo arms of three IPF trials revealed that metformin had no significant effect on disease progression, lung function decline, and mortality in IPF (Spagnolo et al., 2018).”
From Pulmonary fibrosis: Emerging diagnostic and therapeutic strategies (2023) · cites this paper as Spagnolo et al., 2018
Cites
1 retracted
RETRACTED ARTICLE: Type 1 Diabetes Mellitus is an Independent Risk Factor for Pulmonary Fibrosis
Hu, Y., Ma, Z., Guo, Z., et al. (2014) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-014-0068-4 · Cited by 48 · see citing works
RetractedRaghu, G., Collard, H. R., Egan, J. J., Martinez, F. J., Behr, J., Brown, K. K., Colby, T. V., Cordier, J.-F., Flaherty, K. R., Lasky, J. A., et al. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.2009-040gl · Cited by 7,186 · see citing works
A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis.
King, T. E., Bradford, W. Z., Castro-Bernardini, S., Fagan, E. A., Glaspole, I., Glassberg, M. K., Gorina, E., Hopkins, P. M., Kardatzke, D., Lancaster, L., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1402582 · Cited by 3,975 · see citing works
Clinical course and prediction of survival in idiopathic pulmonary fibrosis
Ley, B., Collard, H. R., & King, T. E. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201006-0894ci · Cited by 1,765 · see citing works
Cellular and molecular mechanisms of metformin: an overview
Viollet, B., Guigas, B., Garcia, N. S., Leclerc, J., Foretz, M., & Andreelli, F. (2012) · Clinical Science · doi:10.1042/cs20110386 · Cited by 1,720 · see citing works
Greenland, P. (2007) · Statistics in Medicine · doi:10.1002/sim.2976 · Cited by 1,300 · see citing works
Barr, E. L. M., Zimmet, P. Z., Welborn, T. A., Jolley, D., Magliano, D. J., Dunstan, D. W., Cameron, A. J., Dwyer, T., Taylor, H. R., Tonkin, A. M., et al. (2007) · Circulation · doi:10.1161/circulationaha.106.685628 · Cited by 719 · see citing works
AMPK at the Nexus of Energetics and Aging
Burkewitz, K., Zhang, Y., & Mair, W. B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.002 · Cited by 483 · see citing works
Autophagy in Idiopathic Pulmonary Fibrosis
Patel, A. S., Lin, L., Geyer, A. I., Haspel, J. A., An, C. H., Cao, J., Rosas, I. O., & Morse, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041394 · Cited by 371 · see citing works
Impact of Comorbidities on Mortality in Patients with Idiopathic Pulmonary Fibrosis
Kreuter, M., Ehlers-Tenenbaum, S., Palmowski, K., Bruhwyler, J., Oltmanns, U., Muley, T., Heußel, C. P., Warth, A., Kolb, M. R. J., & Herth, F. J. F. (2016) · PLoS ONE · doi:10.1371/journal.pone.0151425 · Cited by 350 · see citing works
Self-citationInsufficient autophagy in idiopathic pulmonary fibrosis
Araya, J., Kojima, J., Takasaka, N., Ito, S., Fujii, S., Hara, H., Yanagisawa, H., Kobayashi, K., Tsurushige, C., Kawaishi, M., et al. (2012) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00213.2012 · Cited by 326 · see citing works
Metformin attenuates lung fibrosis development via NOX4 suppression
Sato, N., Takasaka, N., Yoshida, M., Tsubouchi, K., Minagawa, S., Araya, J., Saito, N., Fujita, Y., Kurita, Y., Kobayashi, K., et al. (2016) · Respiratory Research · doi:10.1186/s12931-016-0420-x · Cited by 229 · see citing works
Kreuter, M., Swigris, J., Pittrow, D., Geier, S., Klotsche, J., Prasse, A., Wirtz, H., Koschel, D., Andreas, S., Claussen, M., et al. (2017) · Respiratory Research · doi:10.1186/s12931-017-0621-y · Cited by 210 · see citing works
Self-citationMetformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase
Park, C. S., Bang, B., Kwon, H., Moon, K., Kim, T., Lee, K., Moon, H., & Cho, Y. S. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.09.025 · Cited by 208 · see citing works
How does comorbidity influence survival in idiopathic pulmonary fibrosis?
Hyldgaard, C., Hilberg, O., & Bendstrup, E. M. (2014) · Respiratory Medicine · doi:10.1016/j.rmed.2014.01.008 · Cited by 180 · see citing works
Diabetes Mellitus May Increase Risk for Idiopathic Pulmonary Fibrosisa
Enomoto, T., Usuki, J., Azuma, A., et al. (2003) · CHEST Journal · doi:10.1378/chest.123.6.2007 · Cited by 152 · see citing works
Gribbin, J., Hubbard, R., & Smith, C. (2009) · Respiratory Medicine · doi:10.1016/j.rmed.2008.11.001 · Cited by 132 · see citing works
Lu, J., Shi, J., Li, M., Gui, B., Fu, R., Yao, G., Duan, Z., Lv, Z., Yang, Y., Chen, Z., et al. (2015) · Life Sciences · doi:10.1016/j.lfs.2015.01.042 · Cited by 119 · see citing works
Cough in idiopathic pulmonary fibrosis
van Manen, M. J. G., Birring, S. S., Vancheri, C., et al. (2016) · European Respiratory Review · doi:10.1183/16000617.0090-2015 · Cited by 114 · see citing works
Russell, A., Ripamonti, E., & Vancheri, C. (2016) · BMC Pulmonary Medicine · doi:10.1186/s12890-016-0171-y · Cited by 112 · see citing works
Li, L., Huang, W., Li, K., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.6186 · Cited by 93 · see citing works
Effect of statins on disease-related outcomes in patients with idiopathic pulmonary fibrosis
Kreuter, M., Bonella, F., Maher, T. M., Costabel, U., Spagnolo, P., Weycker, D. A., Kirchgaessler, K.-U., & Kolb, M. R. J. (2016) · Thorax · doi:10.1136/thoraxjnl-2016-208819 · Cited by 85 · see citing works
Self-citationIndications of reduced pulmonary function in type 1 (insulin-dependent) diabetes mellitus
Innocenti, F., Fabbri, A., Anichini, R., et al. (1994) · Diabetes Research and Clinical Practice · doi:10.1016/0168-8227(94)90004-3 · Cited by 68 · see citing works
Metformin Attenuates Radiation-Induced Pulmonary Fibrosis in a Murine Model
Wang, J., Wang, Y., Han, J., Mei, H., Yu, D., Ding, Q., Zhang, T., Wu, G., Peng, G., & Lin, Z. (2017) · Radiation Research · doi:10.1667/rr14708.1 · Cited by 54 · see citing works
Metformin attenuates ventilator-induced lung injury
Tsaknis, G., Siempos, I. Ι., Kopterides, P., et al. (2012) · Critical Care · doi:10.1186/cc11439 · Cited by 50 · see citing works
Targeted Therapy for Idiopathic Pulmonary Fibrosis: Where To Now?
Rangarajan, S., Locy, M. L., Luckhardt, T., & Thannickal, V. J. (2016) · Drugs · doi:10.1007/s40265-015-0523-6 · Cited by 50 · see citing works
Lung spirometry parameters and diffusion capacity are decreased in patients with Type 2 diabetes
Klein, O. L., Kalhan, R., Williams, M. V., Tipping, M. D., Lee, J. J., Peng, J., & Smith, L. J. (2011) · Diabetic Medicine · doi:10.1111/j.1464-5491.2011.03394.x · Cited by 48 · see citing works
Kim, Y. J., Park, J.-W., Kyung, S. Y., et al. (2012) · Journal of Korean Medical Science · doi:10.3346/jkms.2012.27.7.756 · Cited by 43 · see citing works
Metformin Reduces Bleomycin-induced Pulmonary Fibrosis in Mice
Choi, S. M., Jang, A.-H., Kim, H., et al. (2016) · Journal of Korean Medical Science · doi:10.3346/jkms.2016.31.9.1419 · Cited by 34 · see citing works
Recent Advances and Future Needs in Interstitial Lung Diseases
Jones, M. G., & Richeldi, L. (2016) · Seminars in Respiratory and Critical Care Medicine · doi:10.1055/s-0036-1580688 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Pulmonary fibrosis: Emerging diagnostic and therapeutic strategies
Selvarajah, B., Platé, M., & Chambers, R. C. (2023) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2023.101227 · Cited by 57 · see citing works
- Authors
- Spagnolo, P., Kreuter, M., Maher, T. M., Wuyts, W., Bonella, F., Corte, T. J., Kopf, S., Weycker, D., Kirchgaessler, K.-U., & Ryerson, C. J.
- Affiliations
- University of Padua (IT)
- Heidelberg University (DE)
- Royal Brompton Hospital (GB)
- Universitair Ziekenhuis Leuven (BE)
- Ruhrlandklinik (DE)
- The University of Sydney (AU)
- University Hospital Heidelberg (DE)
- Policy Analysis (United States) (US)
- F. Hoffmann-La Roche AG (CH)
- University of British Columbia (CA)
- ORCID
- Venue
- Respiration
- Publisher
- S. Karger AG
- Published
- 2018
- Volume
- 96
- Issue
- 4
- Pages
- 314-322
- ISSN
- 0025-7931 (ISSN-L)
- 1423-0356
- OpenAlex
- W2884114811
- Cited by
- 61
- References
- 30
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 12 · 2019: 9 · 2018: 3
- FWCI
- 5.65
- Type
- journal article
- Language
- en
- Open access
- green
- lirias.kuleuven.be
- Locations
- Respiration (publishedVersion)
- PubMed (publishedVersion)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- AstraZeneca
- GlaxoSmithKline
- National Institute for Health and Care Research (CS-2013-13-017)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Keywords
- metformin, idiopathic pulmonary fibrosis, pirfenidone, antidiabetic therapy, disease progression, forced vital capacity decline, 6-minute walk distance, mortality, hospitalization, diabetes mellitus, impaired glucose tolerance, hyperglycemia
- MeSH terms
- Aged, Anti-Inflammatory Agents, Non-Steroidal, Diabetes Mellitus, Female, Humans, Hypoglycemic Agents, Male, Metformin, Middle Aged, Pyridones, Vital Capacity, Disease Progression, Idiopathic Pulmonary Fibrosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
