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The aim of this study is to report baseline data and blinded interim analyses in the register\u2010based randomised clinical trial (\n                      <jats:styled-content style=\"fixed-case\">RRCT<\/jats:styled-content>\n                      )\n                      <jats:styled-content style=\"fixed-case\">SMARTEST<\/jats:styled-content>\n                      , which compares metformin and the\n                      <jats:styled-content style=\"fixed-case\">SGLT2<\/jats:styled-content>\n                      inhibitor dapagliflozin in early\n                      <jats:styled-content style=\"fixed-case\">T2D<\/jats:styled-content>\n                      . We also present learnings from the novel decentralised methodology of this first\n                      <jats:styled-content style=\"fixed-case\">RRCT<\/jats:styled-content>\n                      in diabetes care.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Participants with\n                      <jats:styled-content style=\"fixed-case\">T2D<\/jats:styled-content>\n                      since &lt;4\u2009years and without major cardiovascular or renal disease were included at 36 centres across Sweden between 2019 and 2023 at on\u2010site visits or via remote inclusion using digital informed consent. Participants were randomised 1:1 to open\u2010label dapagliflozin 10\u2009mg\/day or metformin at an individualised dose, and they are followed for 2\u20136\u2009years, with blinding of researchers to endpoints per treatment arm. The composite primary endpoint is time to first event of: myocardial infarction, stroke, heart failure (MACE), appearance or progression of microvascular complications or all\u2010cause death. These events are collected from the Swedish National Diabetes Register and the National Patient Register using automated extraction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 2072 patients, mean age 61.2\u2009years, 39% women, entered randomised treatment. Signs of nephropathy, retinopathy and foot\u2010at\u2010risk were found in 6.1%, 13.2%, and 5.7%, respectively. Hypertension was present in 64.4%, and dyslipidaemia in 57.1%. In blinded interim analyses at a mean follow\u2010up time of 19.0\u2009months, the preliminary event rate of the primary composite endpoint was 11.7\/100 patient\u2010years (py) in the whole study population, mainly driven by microvascular complications. In contrast, rates of cardiovascular events and all\u2010cause death were 0.6 and 0.3\/100 py, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This decentralised\n                      <jats:styled-content style=\"fixed-case\">RRCT<\/jats:styled-content>\n                      in newly onset\n                      <jats:styled-content style=\"fixed-case\">T2D<\/jats:styled-content>\n                      demonstrates a highly feasible option for large\u2010scale trials in the primary care setting, enabling representative participant recruitment. Blinded interim analyses showed a low risk of\n                      <jats:styled-content style=\"fixed-case\">MACE or death<\/jats:styled-content>\n                      , but unexpectedly high rates of microvascular complications. Study completion is event\u2010driven and is expected by January 2026. The study will challenge or reinforce the current metformin paradigm in early\n                      <jats:styled-content style=\"fixed-case\">T2D. (<\/jats:styled-content>\n                      EUDRA\u2010CT number 2019\u2010001046\u201017; EU number 2024\u2010516228\u201033\u201000;\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      Identifier: NCT03982381)\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70320","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T08:06:06Z","timestamp":1764317166000},"page":"1327-1338","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>SGLT2<\/scp>\n                    inhibitor or metformin as standard treatment in early\u2010stage type 2 diabetes? Baseline data in\n                    <scp>SMARTEST<\/scp>\n                    , a novel, decentralised, register\u2010based randomised trial on prevention of diabetic complications"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2639-9481","authenticated-orcid":false,"given":"Jan W.","family":"Eriksson","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Clinical Diabetology and Metabolism Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7920-8909","authenticated-orcid":false,"given":"Giovanni","family":"Fanni","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Clinical Diabetology and Metabolism Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin H.","family":"Lundqvist","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Clinical 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