{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T09:55:00Z","timestamp":1784714100928,"version":"3.55.0"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008713","name":"Diabetes Australia Research Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet Med"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Insulin resistance is an under\u2010recognised metabolic defect and cardiovascular risk factor in Type 1 diabetes. Whether metformin improves hepatic, muscle or adipose tissue insulin sensitivity has not been studied in adults with Type 1 diabetes. We initiated the INTIMET study (INsulin resistance in Type 1 diabetes managed with METformin), a double\u2010blind randomised, placebo\u2010controlled trial to measure the effect of metformin on tissue\u2010specific insulin resistance in adults with Type 1 diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We will study 40 adults aged 20\u201355\u00a0years with Type 1 diabetes (HbA1c <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/dme14564-math-0001.png\" xlink:title=\"urn:x-wiley:07423071:media:dme14564:dme14564-math-0001\"\/>80\u00a0mmol\/mol [9.5%], fasting C\u2010peptide &lt;0.3\u00a0nmol\/L) and 20 age\u2010, gender\u2010 and body mass index (BMI)\u2010matched controls. Insulin sensitivity will be determined by the two\u2010step hyperinsulinaemic\u2010euglycaemic clamp method with deuterated glucose to document liver, muscle and adipose insulin sensitivity. Subjects with Type 1 diabetes will be randomised to metformin extended\u2010release 1500\u00a0mg daily or matched placebo for 26\u00a0weeks. The primary outcome is change in hepatic insulin sensitivity, assessed by change in basal rate of appearance (Ra) of glucose and suppression of endogenous glucose production (EGP) during the low\u2010dose stage of the clamp.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The INTIMET study is the first clinical trial to quantify the impact of metformin on liver, muscle and adipose insulin resistance in adults with Type 1 diabetes. This study may identify factors that predict an individual's response to metformin in Type 1 diabetes. Trial Registration: ACTRN12619001440112.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.14564","type":"journal-article","created":{"date-parts":[[2021,3,28]],"date-time":"2021-03-28T00:40:30Z","timestamp":1616892030000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Insulin resistance in type 1 diabetes managed with metformin (INTIMET): Study protocol of a double\u2010blind placebo\u2010controlled, randomised trial"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8559-8387","authenticated-orcid":false,"given":"Jennifer R.","family":"Snaith","sequence":"first","affiliation":[{"name":"Healthy Ageing Garvan Institute of Medical Research Darlinghurst NSW Australia"},{"name":"St Vincent's Clinical School University of New South Wales Sydney NSW Australia"},{"name":"Department of Diabetes and Endocrinology St Vincent's Hospital Sydney Darlinghurst NSW Australia"},{"name":"Department of Diabetes and Endocrinology Westmead Hospital Westmead NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9422-7852","authenticated-orcid":false,"given":"Dorit","family":"Samocha\u2010Bonet","sequence":"additional","affiliation":[{"name":"Healthy Ageing Garvan Institute of Medical Research Darlinghurst NSW Australia"},{"name":"St Vincent's Clinical School University of New South Wales Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Evans","sequence":"additional","affiliation":[{"name":"Healthy Ageing Garvan Institute of Medical Research Darlinghurst NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3337-0692","authenticated-orcid":false,"given":"Zhixin","family":"Liu","sequence":"additional","affiliation":[{"name":"Stats Central University of New South Wales Sydney NSW Australia"},{"name":"Mark Wainwright Analytical Centre University of New South Wales Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1599-017X","authenticated-orcid":false,"given":"Greg","family":"Kowalski","sequence":"additional","affiliation":[{"name":"Institute for Physical Activity and Nutrition School of Exercise and Nutrition Sciences Deakin University Geelong Vic. 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