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Intensive insulin therapy prevents\n                      <jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content>\n                      complications but is constrained by hypoglycaemia and weight gain. Adjunct metformin reduces insulin dose requirement and stabilizes weight but there are no data on its cardiovascular effects. We have therefore initiated an international double\u2010blind, randomized, placebo\u2010controlled trial (\n                      <jats:styled-content style=\"fixed-case\">REMOVAL<\/jats:styled-content>\n                      :\n                      <jats:styled-content style=\"fixed-case\">REducing<\/jats:styled-content>\n                      with\n                      <jats:styled-content style=\"fixed-case\">MetfOrmin V<\/jats:styled-content>\n                      ascular\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      dverse\n                      <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>\n                      esions in type 1 diabetes) to examine whether metformin reduces progression of atherosclerosis in adults with\n                      <jats:styled-content style=\"fixed-case\">T1D<\/jats:styled-content>\n                      . Individuals \u226540\u2009years of age with\n                      <jats:styled-content style=\"fixed-case\">T1D<\/jats:styled-content>\n                      for \u22655\u2009years are eligible if they have \u22653 of 10 specified\n                      <jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content>\n                      risk factors. The enrolment target is 500 participants in 17 international centres.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      After 12\u2009weeks of single\u2010blind placebo\u2010controlled run\u2010in, participants with \u2265 70% adherence are randomized to metformin or matching placebo for 3\u2009years with insulin titrated towards\n                      <jats:styled-content style=\"fixed-case\">HbA1c<\/jats:styled-content>\n                      7.0% (53\u2009mmol\/mol). The primary endpoint is progression of averaged mean far wall common carotid intima\u2010media thickness (\n                      <jats:styled-content style=\"fixed-case\">cIMT<\/jats:styled-content>\n                      ) measured by ultrasonography at baseline, 12, 24 and 36\u2009months. This design provides 90% power to detect a mean difference of 0.0167\u2009mm in\n                      <jats:styled-content style=\"fixed-case\">cIMT<\/jats:styled-content>\n                      progression between treatment arms (\u03b1\u2009=\u20090.05), assuming that up to 20% withdraw or discontinue treatment. Other endpoints include\n                      <jats:styled-content style=\"fixed-case\">HbA1c<\/jats:styled-content>\n                      , weight,\n                      <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\n                      cholesterol, insulin requirement, progression of retinopathy, endothelial function and frequency of hypoglycaemia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">REMOVAL<\/jats:styled-content>\n                      is the largest clinical trial of adjunct metformin therapy in\n                      <jats:styled-content style=\"fixed-case\">T1D<\/jats:styled-content>\n                      to date and will provide clinically meaningful information on its potential to impact\n                      <jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content>\n                      disease and other complications.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.12840","type":"journal-article","created":{"date-parts":[[2016,12,9]],"date-time":"2016-12-09T08:44:44Z","timestamp":1481273084000},"page":"509-516","source":"Crossref","is-referenced-by-count":34,"title":["Metformin in adults with type 1 diabetes:\n                    <scp>D<\/scp>\n                    esign and methods of\n                    <scp>REducing<\/scp>\n                    with\n                    <scp>MetfOrmin V<\/scp>\n                    ascular\n                    <scp>A<\/scp>\n                    dverse\n                    <scp>L<\/scp>\n                    esions (\n                    <scp>REMOVAL<\/scp>\n                    ):\n                    <scp>A<\/scp>\n                    n international multicentre trial"],"prefix":"10.1111","volume":"19","author":[{"given":"John R.","family":"Petrie","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nish","family":"Chaturvedi","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Ford","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Hramiak","sequence":"additional","affiliation":[{"name":"St Joseph's Health Care  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alun D.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia J.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"NHMRC Clinical Trials Centre University of Sydney  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"E. 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