{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:12:22Z","timestamp":1793261542482,"version":"4.5.0"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1180736"],"award-info":[{"award-number":["APP1180736"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011371","name":"Royal Australasian College of Surgeons","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100011371","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020127","name":"the Australian and New Zealand Society for Vascular Surgery","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100020127","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Townsville Hospital and Health Services","id":[{"id":"https:\/\/ror.org\/021zqhw10","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001505","name":"the Health Research Council of New Zealand","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35\u2009mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500\u2009mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      Australian Clinical Trials\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.australianclinicaltrials.gov.au\/anzctr\/trial\/ACTRN12618001707257\">ACTRN12618001707257<\/jats:ext-link>\n                      . Registered on 16 October 2018\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-021-05915-0","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T06:05:55Z","timestamp":1640585155000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Protocol for the Metformin Aneurysm Trial (MAT): a placebo-controlled randomised trial testing whether metformin reduces the risk of serious complications of abdominal aortic aneurysm"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5779-8848","authenticated-orcid":false,"given":"Jonathan","family":"Golledge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Arnott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Moxon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Monaghan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Norman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Roake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Bown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Neal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,27]]},"reference":[{"issue":"9963","key":"5915_CR1","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/S0140-6736(14)61682-2","volume":"385","author":"GBD Mortality","year":"2015","unstructured":"Mortality GBD. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385(9963):117\u201371.","journal-title":"Lancet."},{"issue":"19","key":"5915_CR2","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1056\/NEJMoa013527","volume":"346","author":"JT Powell","year":"2002","unstructured":"United Kingdom Small Aneurysm Trial Participants, Powell JT, Brady AR, Brown LC, Fowkes FG, Greenhalgh RM, et al. Long-term outcomes of immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346(19):1445\u201352.","journal-title":"N Engl J Med."},{"issue":"22","key":"5915_CR3","doi-asserted-by":"publisher","first-page":"2968","DOI":"10.1001\/jama.287.22.2968","volume":"287","author":"FA Lederle","year":"2002","unstructured":"Lederle FA, Johnson GR, Wilson SE, Ballard DJ, Jordan WD Jr, Blebea J, et al. Rupture rate of large abdominal aortic aneurysms in patients refusing or unfit for elective repair. JAMA. 2002;287(22):2968\u201372.","journal-title":"JAMA."},{"key":"5915_CR4","doi-asserted-by":"crossref","unstructured":"Chaikof EL, Dalman RL, Eskandari MK, Jackson BM, Lee WA, Mansour MA, et al. The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm. J Vasc Surg. 2018;67(1):2-77.e2.","DOI":"10.1016\/j.jvs.2017.10.044"},{"issue":"1","key":"5915_CR5","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ejvs.2018.09.020","volume":"57","author":"A Wanhainen","year":"2019","unstructured":"Wanhainen A, Verzini F, Van Herzeele I, Allaire E, Bown M, Cohnert T, et al. Editor\u2019s choice - European Society for Vascular Surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms. Eur J Vasc Endovasc Surg. 2019;57(1):8\u201393.","journal-title":"Eur J Vasc Endovasc Surg."},{"issue":"2","key":"5915_CR6","volume":"2015","author":"G Filardo","year":"2015","unstructured":"Filardo G, Powell JT, Martinez MA, Ballard DJ. Surgery for small asymptomatic abdominal aortic aneurysms. Cochrane Database Syst Rev. 2015;2015(2):CD001835.","journal-title":"Cochrane Database Syst Rev"},{"issue":"1","key":"5915_CR7","first-page":"52","volume":"18","author":"JS Lindholt","year":"1999","unstructured":"Lindholt JS, Henneberg EW, Juul S, Fasting H. Impaired results of a randomised double blinded clinical trial of propranolol versus placebo on the expansion rate of small abdominal aortic aneurysms. Int Angiol. 1999;18(1):52\u20137.","journal-title":"Int Angiol."},{"issue":"1","key":"5915_CR8","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1067\/mva.2002.121308","volume":"35","author":"PAT Investigators","year":"2002","unstructured":"Investigators PAT. Propranolol for small abdominal aortic aneurysms: results of a randomized trial. J Vasc Surg. 2002;35(1):72\u20139.","journal-title":"J Vasc Surg."},{"issue":"42","key":"5915_CR9","doi-asserted-by":"publisher","first-page":"3213","DOI":"10.1093\/eurheartj\/ehw257","volume":"37","author":"CD Bicknell","year":"2016","unstructured":"Bicknell CD, Kiru G, Falaschetti E, Powell JT, Poulter NR, Collaborators A. An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomized placebo-controlled trial (AARDVARK). Eur Heart J. 2016;37(42):3213\u201321.","journal-title":"Eur Heart J."},{"issue":"12","key":"5915_CR10","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1001\/jamacardio.2020.3524","volume":"5","author":"J Golledge","year":"2020","unstructured":"Golledge J, Pinchbeck J, Tomee SM, Rowbotham SE, Singh TP, Moxon JV, et al. Efficacy of telmisartan to slow growth of small abdominal aortic aneurysms: a randomized clinical trial. JAMA Cardiol. 2020;5(12):1374\u201381.","journal-title":"JAMA Cardiol."},{"issue":"1","key":"5915_CR11","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.jvs.2008.12.048","volume":"50","author":"L Karlsson","year":"2009","unstructured":"Karlsson L, Gnarpe J, Bergqvist D, Lindback J, Parsson H. The effect of azithromycin and Chlamydophilia pneumonia infection on expansion of small abdominal aortic aneurysms--a prospective randomized double-blind trial. J Vasc Surg. 2009;50(1):23\u20139.","journal-title":"J Vasc Surg."},{"issue":"5","key":"5915_CR12","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1177\/1538574409335037","volume":"43","author":"A H\u00f8gh","year":"2009","unstructured":"H\u00f8gh A, Vammen S, Ostergaard L, Joensen JB, Henneberg EW, Lindholt JS. Intermittent roxithromycin for preventing progression of small abdominal aortic aneurysms: long-term results of a small clinical trial. Vasc Endovascular Surg. 2009;43(5):452\u20136.","journal-title":"Vasc Endovascular Surg."},{"issue":"4","key":"5915_CR13","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1067\/mva.2001.117891","volume":"34","author":"M Mosorin","year":"2001","unstructured":"Mosorin M, Juvonen J, Biancari F, Satta J, Surcel H-M, Leinonen M, et al. Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: a randomized, double-blind, placebo-controlled pilot study. J Vasc Surg. 2001;34(4):606\u201310.","journal-title":"J Vasc Surg"},{"issue":"20","key":"5915_CR14","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1001\/jama.2020.5230","volume":"323","author":"BT Baxter","year":"2020","unstructured":"Baxter BT, Matsumura J, Curci JA, McBride R, Larson L, Blackwelder W, et al. Effect of doxycycline on aneurysm growth among patients with small infrarenal abdominal aortic aneurysms: a randomized clinical trial. JAMA. 2020;323(20):2029\u201338.","journal-title":"JAMA."},{"issue":"12","key":"5915_CR15","doi-asserted-by":"publisher","first-page":"815","DOI":"10.7326\/0003-4819-159-12-201312170-00007","volume":"159","author":"CA Meijer","year":"2013","unstructured":"Meijer CA, Stijnen T, Wasser MN, Hamming JF, van Bockel JH, Lindeman JH, et al. Doxycycline for stabilization of abdominal aortic aneurysms: a randomized trial. Ann Intern Med. 2013;159(12):815\u201323.","journal-title":"Ann Intern Med."},{"issue":"8","key":"5915_CR16","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1046\/j.0007-1323.2001.01845.x","volume":"88","author":"S Vammen","year":"2001","unstructured":"Vammen S, Lindholt JS, Ostergaard L, Fasting H, Henneberg EW. Randomized double-blind controlled trial of roxithromycin for prevention of abdominal aortic aneurysm expansion. Br J Surg. 2001;88(8):1066\u201372.","journal-title":"Br J Surg."},{"issue":"8","key":"5915_CR17","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1002\/bjs.9824","volume":"102","author":"H Sillesen","year":"2015","unstructured":"Sillesen H, Eldrup N, Hultgren R, Lindeman J, Bredahl K, Thompson M, et al. Randomized clinical trial of mast cell inhibition in patients with a medium-sized abdominal aortic aneurysm. Br J Surg. 2015;102(8):894\u2013901.","journal-title":"Br J Surg"},{"issue":"2","key":"5915_CR18","first-page":"450","volume":"116","author":"A Wanhainen","year":"2020","unstructured":"Wanhainen A, Mani K, Kullberg J, Svensj\u00f6 S, Bersztel A, Karlsson L, et al. The effect of ticagrelor on growth of small abdominal aortic aneurysms-a randomized controlled trial. Cardiovasc Res. 2020;116(2):450\u20136.","journal-title":"Cardiovasc Res"},{"key":"5915_CR19","doi-asserted-by":"crossref","unstructured":"Pinchbeck JL, Moxon JV, Rowbotham SE, Bourke M, Lazzaroni S, Morton SK, et al. Randomized placebo-controlled trial assessing the effect of 24-week fenofibrate therapy on circulating markers of abdominal aortic aneurysm: outcomes from the FAME-2 trial. J Am Heart Assoc 2018;7(19):e009866.","DOI":"10.1161\/JAHA.118.009866"},{"issue":"1","key":"5915_CR20","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/joim.12958","volume":"288","author":"J Golledge","year":"2020","unstructured":"Golledge J, Moxon JV, Singh TP, Bown MJ, Mani K, Wanhainen A. Lack of an effective drug therapy for abdominal aortic aneurysm. J Intern Med. 2020;288(1):6\u201322.","journal-title":"J Intern Med."},{"issue":"4","key":"5915_CR21","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/s41569-018-0114-9","volume":"16","author":"J Golledge","year":"2019","unstructured":"Golledge J. Abdominal aortic aneurysm: update on pathogenesis and medical treatments. Nat Rev Cardiol. 2019;16(4):225\u201342.","journal-title":"Nat Rev Cardiol."},{"key":"5915_CR22","doi-asserted-by":"crossref","unstructured":"Golledge J, Norman PE, Murphy MP, Dalman RL. Challenges and opportunities in limiting abdominal aortic aneurysm growth. J Vasc Surg. 2017;65(1):225-33. .","DOI":"10.1016\/j.jvs.2016.08.003"},{"key":"5915_CR23","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.ijcard.2016.07.016","volume":"221","author":"J Xiong","year":"2016","unstructured":"Xiong J, Wu Z, Chen C, Wei Y, Guo W. Association between diabetes and prevalence and growth rate of abdominal aortic aneurysms: a meta-analysis. Int J Cardiol. 2016;221:484\u201395.","journal-title":"Int J Cardiol"},{"issue":"5","key":"5915_CR24","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1093\/eurheartj\/ehm557","volume":"29","author":"J Golledge","year":"2008","unstructured":"Golledge J, Karan M, Moran CS, Muller J, Clancy P, Dear AE, et al. Reduced expansion rate of abdominal aortic aneurysms in patients with diabetes may be related to aberrant monocyte-matrix interactions. Eur Heart J. 2008;29(5):665\u201372.","journal-title":"Eur Heart J."},{"issue":"9","key":"5915_CR25","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1056\/NEJMoa1008862","volume":"364","author":"S Rao Kondapally Seshasai","year":"2011","unstructured":"Rao Kondapally Seshasai S, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011;364(9):829\u201341.","journal-title":"N Engl J Med"},{"issue":"3","key":"5915_CR26","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1161\/CIRCULATIONAHA.119.040398","volume":"140","author":"DR Morris","year":"2019","unstructured":"Morris DR, Sherliker P, Clack R, Preiss D, Lam KBH, Carter J, et al. Opposite associations of aortic aneurysm with blood glucose and with diabetes mellitus. Circulation. 2019;140(3):264\u20136.","journal-title":"Circulation."},{"issue":"1","key":"5915_CR27","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.jvs.2016.02.020","volume":"64","author":"N Fujimura","year":"2016","unstructured":"Fujimura N, Xiong J, Kettler EB, Xuan H, Glover KJ, Mell MW, et al. Metformin treatment status and abdominal aortic aneurysm disease progression. J Vasc Surg. 2016;64(1):46\u201354.","journal-title":"J Vasc Surg."},{"issue":"54","key":"5915_CR28","doi-asserted-by":"publisher","first-page":"92827","DOI":"10.18632\/oncotarget.21608","volume":"8","author":"L Yang","year":"2017","unstructured":"Yang L, Shen L, Gao P, Li G, He Y, Wang M, et al. Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms. Oncotarget. 2017;8(54):92827\u201340.","journal-title":"Oncotarget"},{"issue":"6","key":"5915_CR29","doi-asserted-by":"publisher","first-page":"2028","DOI":"10.2337\/db14-1225","volume":"64","author":"SB Vasamsetti","year":"2015","unstructured":"Vasamsetti SB, Karnewar S, Kanugula AK, Thatipalli AR, Kumar JM, Kotamraju S. Metformin inhibits monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis. Diabetes. 2015;64(6):2028\u201341.","journal-title":"Diabetes"},{"key":"5915_CR30","unstructured":"Unosson J, W\u00e5gs\u00e4ter D, Bjarneg\u00e5rd N, De Basso R, Welander M, Mani K, et al. Metformin prescription associated with reduced abdominal aortic aneurysm growth rate and reduced chemokine expression in a Swedish cohort. Ann Vasc Surg. 2020:S0890-5096(20)30540-9."},{"issue":"3","key":"5915_CR31","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/j.jvs.2018.06.194","volume":"69","author":"NK Itoga","year":"2019","unstructured":"Itoga NK, Rothenberg KA, Suarez P, Ho TV, Mell MW, Xu B, et al. Metformin prescription status and abdominal aortic aneurysm disease progression in the U.S. veteran population. J Vasc Surg. 2019;69(3):710\u20136.","journal-title":"J Vasc Surg."},{"issue":"11","key":"5915_CR32","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1002\/bjs.10587","volume":"104","author":"J Golledge","year":"2017","unstructured":"Golledge J, Moxon J, Pinchbeck J, Anderson G, Rowbotham S, Jenkins J, et al. Association between metformin prescription and growth rates of abdominal aortic aneurysms. Br J Surg. 2017;104(11):1486\u201393.","journal-title":"Br J Surg"},{"issue":"14","key":"5915_CR33","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1056\/NEJMoa1709118","volume":"377","author":"JW Eikelboom","year":"2017","unstructured":"Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377(14):1319\u201330.","journal-title":"N Engl J Med."},{"issue":"9","key":"5915_CR34","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2015-008531","volume":"5","author":"CF Christiansen","year":"2015","unstructured":"Christiansen CF, Ehrenstein V, Heide-Jorgensen U, Skovbo S, Norrelund H, Sorensen HT, et al. Metformin initiation and renal impairment: a cohort study in Denmark and the UK. BMJ Open. 2015;5(9):e008531.","journal-title":"BMJ Open."},{"issue":"2","key":"5915_CR35","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.atherosclerosis.2013.11.034","volume":"232","author":"J Golledge","year":"2014","unstructured":"Golledge J, Ewels C, Muller R, Walker PJ. Association of chronic kidney disease categories defined with different formulae with major adverse events in patients with peripheral vascular disease. Atherosclerosis. 2014;232(2):289\u201397.","journal-title":"Atherosclerosis."},{"key":"5915_CR36","volume-title":"National guidelines for diabetes","author":"S Colagiuri","year":"2009","unstructured":"Colagiuri S. National guidelines for diabetes. Diabetes Australia\/NHMRC: Canberra; 2009."},{"issue":"4 Suppl","key":"5915_CR37","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1016\/j.jvs.2009.07.002","volume":"50","author":"EL Chaikof","year":"2009","unstructured":"Chaikof EL, Brewster DC, Dalman RL, Makaroun MS, Illig KA, Sicard GA, et al. The care of patients with an abdominal aortic aneurysm: the Society for Vascular Surgery practice guidelines. J Vasc Surg. 2009;50(4 Suppl):S2\u201349.","journal-title":"J Vasc Surg."},{"issue":"Suppl 1","key":"5915_CR38","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1016\/j.ejvs.2010.09.011","volume":"41","author":"FL Moll","year":"2011","unstructured":"Moll FL, Powell JT, Fraedrich G, Verzini F, Haulon S, Waltham M, et al. Management of abdominal aortic aneurysms clinical practice guidelines of the European Society for Vascular Surgery. Eur J Vasc Endovasc Surg. 2011;41(Suppl 1):S1\u2013S58.","journal-title":"Eur J Vasc Endovasc Surg."},{"issue":"11","key":"5915_CR39","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1002\/bjs.10587","volume":"104","author":"J Golledge","year":"2017","unstructured":"Golledge J, Moxon J, Pinchbeck J, Anderson G, Rowbotham S, Jenkins J, et al. Association between metformin prescription and growth rates of abdominal aortic aneurysms. Br J Surg. 2017;104(11):1486\u201393.","journal-title":"Br J Surg."},{"key":"5915_CR40","doi-asserted-by":"crossref","unstructured":"Pinchbeck JL, Moxon JV, Rowbotham SE, Bourke M, Lazzaroni S, Morton SK, et al. Randomized placebo-controlled trial assessing the effect of 24-week fenofibrate therapy on circulating markers of abdominal aortic aneurysm: outcomes from the FAME-2 trial. J Am Heart Assoc. 2018;7(19):e009866.","DOI":"10.1161\/JAHA.118.009866"},{"issue":"5","key":"5915_CR41","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1136\/annrheumdis-2018-214656","volume":"78","author":"N Vazirpanah","year":"2019","unstructured":"Vazirpanah N, Ottria A, van der Linden M, Wichers CGK, Schuiveling M, van Lochem E, et al. mTOR inhibition by metformin impacts monosodium urate crystal-induced inflammation and cell death in gout: a prelude to a new add-on therapy? Ann Rheum Dis. 2019;78(5):663\u201371.","journal-title":"Ann Rheum Dis."},{"issue":"1","key":"5915_CR42","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.ejvs.2018.07.035","volume":"57","author":"J Golledge","year":"2019","unstructured":"Golledge J, Morris DR, Pinchbeck J, Rowbotham S, Jenkins J, Bourke M, et al. Editor\u2019s choice - Metformin prescription is associated with a reduction in the combined incidence of surgical repair and rupture related mortality in patients with abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 2019;57(1):94\u2013101.","journal-title":"Eur J Vasc Endovasc Surg."},{"issue":"3","key":"5915_CR43","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.ejvs.2005.05.043","volume":"30","author":"P Cao","year":"2005","unstructured":"Cao P. Caesar Trial Collaborators. Comparison of surveillance vs Aortic Endografting for Small Aneurysm Repair (CAESAR) trial: study design and progress. Eur J Vasc Endovasc Surg. 2005;30(3):245\u201351.","journal-title":"Eur J Vasc Endovasc Surg."},{"issue":"1","key":"5915_CR44","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1186\/s13063-016-1354-9","volume":"17","author":"T Aung","year":"2016","unstructured":"Aung T, Haynes R, Barton J, Cox J, Murawska A, Murphy K, et al. Cost-effective recruitment methods for a large randomised trial in people with diabetes: A Study of Cardiovascular Events iN Diabetes (ASCEND). Trials. 2016;17(1):286.","journal-title":"Trials."},{"issue":"6","key":"5915_CR45","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1177\/0272989X13503499","volume":"34","author":"R Norman","year":"2014","unstructured":"Norman R, Viney R, Brazier J, Burgess L, Cronin P, King M, et al. Valuing SF-6D health states using a discrete choice experiment. Med Decis Making. 2014;34(6):773\u201386.","journal-title":"Med Decis Making."},{"issue":"1","key":"5915_CR46","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s41687-019-0119-0","volume":"3","author":"J Romaine","year":"2019","unstructured":"Romaine J, Peach G, Thompson M, Hinchliffe RJ, Bradley C. Psychometric validation of three new condition-specific questionnaires to assess quality of life, symptoms and treatment satisfaction of patients with aortic aneurysm. J Patient Rep Outcomes. 2019;3(1):29.","journal-title":"J Patient Rep Outcomes."},{"key":"5915_CR47","doi-asserted-by":"publisher","first-page":"c332","DOI":"10.1136\/bmj.c332","volume":"340","author":"KF Schulz","year":"2010","unstructured":"Schulz KF, Altman DG, Moher D, Group C. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332.","journal-title":"BMJ."},{"issue":"1","key":"5915_CR48","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.gheart.2013.12.009","volume":"9","author":"UK Sampson","year":"2014","unstructured":"Sampson UK, Norman PE, Fowkes FG, Aboyans V, Song Y, Harrell FE Jr, et al. Estimation of global and regional incidence and prevalence of abdominal aortic aneurysms 1990 to 2010. Glob Heart. 2014;9(1):159\u201370.","journal-title":"Glob Heart."},{"issue":"6","key":"5915_CR49","doi-asserted-by":"publisher","first-page":"526","DOI":"10.23736\/S0392-9590.17.03889-5","volume":"36","author":"R Lee","year":"2017","unstructured":"Lee R, Jones A, Cassimjee I, Handa A. Patients\u2019 opinions regarding research and management of abdominal aortic aneurysms. Int Angiol. 2017;36(6):526\u201330.","journal-title":"Int Angiol."},{"key":"5915_CR50","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.ijcard.2017.06.058","volume":"245","author":"R Lee","year":"2017","unstructured":"Lee R, Jones A, Cassimjee I, Handa A, Oxford Abdominal Aortic Aneurysm S. International opinion on priorities in research for small abdominal aortic aneurysms and the potential path for research to impact clinical management. Int J Cardiol. 2017;245:253\u20135.","journal-title":"Int J Cardiol"},{"issue":"1","key":"5915_CR51","doi-asserted-by":"publisher","first-page":"37","DOI":"10.5694\/mja2.50239","volume":"211","author":"C Tanner","year":"2019","unstructured":"Tanner C, Wang G, Liu N, Andrikopoulos S, Zajac JD, Ekinci EI. Metformin: time to review its role and safety in chronic kidney disease. Med J Aust. 2019;211(1):37\u201342.","journal-title":"Med J Aust."},{"issue":"15","key":"5915_CR52","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1001\/jama.2014.3315","volume":"311","author":"CP Lexis","year":"2014","unstructured":"Lexis CP, van der Horst IC, Lipsic E, Wieringa WG, de Boer RA, van den Heuvel AF, et al. Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial. JAMA. 2014;311(15):1526\u201335.","journal-title":"JAMA."},{"issue":"1","key":"5915_CR53","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2015-000090","volume":"3","author":"CP Lexis","year":"2015","unstructured":"Lexis CP, van der Horst-Schrivers AN, Lipsic E, Valente MA, Muller Kobold AC, de Boer RA, et al. The effect of metformin on cardiovascular risk profile in patients without diabetes presenting with acute myocardial infarction: data from the Glycometabolic Intervention as adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) trial. BMJ Open Diabetes Res Care. 2015;3(1):e000090.","journal-title":"BMJ Open Diabetes Res Care."},{"issue":"4","key":"5915_CR54","first-page":"261","volume":"21","author":"SS Lim","year":"2011","unstructured":"Lim SS, Norman RJ, Clifton PM, Noakes M. The effect of comprehensive lifestyle intervention or metformin on obesity in young women. Nutr Metab Cardiovasc Dis. 2011;21(4):261\u20138.","journal-title":"Nutr Metab Cardiovasc Dis."},{"issue":"12","key":"5915_CR55","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1177\/0269881115613519","volume":"29","author":"VA de Silva","year":"2015","unstructured":"de Silva VA, Dayabandara M, Wijesundara H, Henegama T, Gunewardena H, Suraweera C, et al. Metformin for treatment of antipsychotic-induced weight gain in a South Asian population with schizophrenia or schizoaffective disorder: a double blind, randomized, placebo controlled study. J Psychopharmacol. 2015;29(12):1255\u201361.","journal-title":"J Psychopharmacol."},{"issue":"3","key":"5915_CR56","doi-asserted-by":"publisher","first-page":"290","DOI":"10.20945\/2359-3997000000251","volume":"64","author":"IBD Nascimento","year":"2020","unstructured":"Nascimento IBD, Sales WB, Dienstmann G, Souza MLR, Fleig R, Silva JC. Metformin for prevention of cesarean delivery and large-for-gestational-age newborns in non-diabetic obese pregnant women: a randomized clinical trial. Arch Endocrinol Metab. 2020;64(3):290\u20137.","journal-title":"Arch Endocrinol Metab."},{"issue":"4","key":"5915_CR57","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/S2213-8587(20)30021-8","volume":"8","author":"I Pernicova","year":"2020","unstructured":"Pernicova I, Kelly S, Ajodha S, Sahdev A, Bestwick JP, Gabrovska P, et al. Metformin to reduce metabolic complications and inflammation in patients on systemic glucocorticoid therapy: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial. Lancet Diabetes Endocrinol. 2020;8(4):278\u201391.","journal-title":"Lancet Diabetes Endocrinol."},{"issue":"12","key":"5915_CR58","volume":"12","author":"KS Madsen","year":"2019","unstructured":"Madsen KS, Chi Y, Metzendorf MI, Richter B, Hemmingsen B. Metformin for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2019;12(12):CD008558.","journal-title":"Cochrane Database Syst Rev."},{"issue":"11","key":"5915_CR59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0207947","volume":"13","author":"M Solym\u00e1r","year":"2018","unstructured":"Solym\u00e1r M, Ivic I, P\u00f3t\u00f3 L, Hegyi P, Garami A, Hartmann P, et al. Metformin induces significant reduction of body weight, total cholesterol and LDL levels in the elderly - a meta-analysis. PLoS One. 2018;13(11):e0207947.","journal-title":"PLoS One."},{"issue":"5","key":"5915_CR60","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1161\/CIRCULATIONAHA.117.031735","volume":"137","author":"G Rena","year":"2018","unstructured":"Rena G, Lang CC. Repurposing metformin for cardiovascular disease. Circulation. 2018;137(5):422\u20134.","journal-title":"Circulation."},{"key":"5915_CR61","doi-asserted-by":"publisher","first-page":"851","DOI":"10.3389\/fendo.2019.00851","volume":"10","author":"F Bost","year":"2019","unstructured":"Bost F, Rena G, Viollet B. Editorial: Metformin: beyond diabetes. Front Endocrinol (Lausanne). 2019;10:851.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"5915_CR62","unstructured":"Neumayer C, Eilenberg W. Metformin therapy in non-diabetic AAA patients (MetAAA). 2018 https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03507413?term=metformin&cond=Abdominal+Aortic+Aneurysm&draw=2&rank=2. Accessed 10 Novermber 2021."},{"key":"5915_CR63","doi-asserted-by":"publisher","DOI":"10.15420\/ver.2020.03","volume":"3","author":"R Dalman","year":"2020","unstructured":"Dalman R, Lu Y, Mahaffey K, Chase A, Stern J, Chang R. Background and proposed design for a metformin abdominal aortic aneurysm supression trial. Vascular & Endovascular Review. 2020;3:e08.","journal-title":"Vascular & Endovascular Review"},{"issue":"2","key":"5915_CR64","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1161\/ATVBAHA.115.306538","volume":"36","author":"A Wanhainen","year":"2016","unstructured":"Wanhainen A, Mani K, Golledge J. Surrogate markers of abdominal aortic aneurysm progression. Arterioscler Thromb Vasc Biol. 2016;36(2):236\u201344.","journal-title":"Arterioscler Thromb Vasc Biol."},{"issue":"1","key":"5915_CR65","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.ejrad.2009.12.018","volume":"79","author":"A Parr","year":"2011","unstructured":"Parr A, Jayaratne C, Buttner P, Golledge J. Comparison of volume and diameter measurement in assessing small abdominal aortic aneurysm expansion examined using computed tomographic angiography. Eur J Radiol. 2011;79(1):42\u20137.","journal-title":"Eur J Radiol"},{"issue":"18","key":"5915_CR66","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/hta22180","volume":"22","author":"SJ Griffin","year":"2018","unstructured":"Griffin SJ, Bethel MA, Holman RR, Khunti K, Wareham N, Brierley G, et al. Metformin in non-diabetic hyperglycaemia: the GLINT feasibility RCT. Health Technol Assess. 2018;22(18):1\u201364.","journal-title":"Health Technol Assess."}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-021-05915-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-021-05915-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-021-05915-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T04:07:35Z","timestamp":1676088455000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-021-05915-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,27]]},"references-count":66,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["5915"],"URL":"https:\/\/doi.org\/10.1186\/s13063-021-05915-0","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,27]]},"assertion":[{"value":"28 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"MAT has been approved by central ethics committees in Australia and New Zealand. Written, informed consent to participate will be obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate {24}"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication {32}"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"962"}}