{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T22:35:18Z","timestamp":1785191718441,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 133701"],"award-info":[{"award-number":["MOP 133701"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To test the hypothesis that the addition of periodic courses of short\u2010term intensive insulin therapy (IIT) could enhance the effect of metformin (MET) maintenance therapy on preservation of beta\u2010cell function following induction IIT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this multicentre, randomized controlled trial, 108 adults with type 2 diabetes (median 1.3\u2009years\u2019 duration; HbA1c 6.6%\u2009\u00b1\u20090.6%) were randomized to 3\u2009weeks of induction IIT (glargine, lispro) followed by MET maintenance, either with or without periodic 2\u2010week courses of IIT every 3 months for 2\u2009years. Beta\u2010cell function was assessed by the Insulin Secretion Sensitivity Index\u20102 (ISSI\u20102) at an oral glucose tolerance test every 3 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In both arms, induction IIT increased ISSI\u20102, improved whole\u2010body insulin sensitivity and reduced hepatic insulin resistance (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009\u2264\u2009.0004). The primary outcome of baseline\u2010adjusted ISSI\u20102 at 2\u2009years was not improved by the addition of intermittent IIT (MET + IIT) and was slightly higher in the MET arm (baseline\u2010adjusted difference\u2009\u221235 [95% CI: \u221266, \u20133]), with three additional beta\u2010cell measures showing no significant differences. Baseline\u2010adjusted HbA1c at 2\u2009years did not differ between MET and MET + IIT (6.3%\u2009\u00b1\u20090.1% vs. 6.4%\u2009\u00b1\u20090.1%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.46), with 32.6% of participants in each arm maintaining HbA1c of\u00a06.0% or less at 2\u2009years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although initial induction IIT induces metabolic improvement, subsequent repeat courses of IIT every 3 months do not further enhance the effect of MET maintenance therapy on beta\u2010cell function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14421","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T08:24:34Z","timestamp":1620375874000},"page":"1926-1935","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Short\u2010term intensive insulin as induction and maintenance therapy for the preservation of beta\u2010cell function in early type 2 diabetes (\n                    <scp>RESET\u2010IT Main<\/scp>\n                    ): A 2\u2010year randomized controlled trial"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1989-027X","authenticated-orcid":false,"given":"Ravi","family":"Retnakaran","sequence":"first","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital  Toronto Ontario Canada"},{"name":"Division of Endocrinology University of Toronto  Toronto Ontario Canada"},{"name":"Lunenfeld\u2010Tanenbaum Research Institute, 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