{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:38:59Z","timestamp":1792471139966,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100022690","name":"JDRF","doi-asserted-by":"publisher","award":["3\u2010SRA\u20102019\u2010669\u2010M\u2010B"],"award-info":[{"award-number":["3\u2010SRA\u20102019\u2010669\u2010M\u2010B"]}],"id":[{"id":"10.13039\/100022690","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":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Attaining target glycaemia can be a challenge in Type 1 Diabetes (T1D) due to insulin\u2010induced weight gain. Adjunct therapy with modern glucose\u2010lowering agents developed for type 2 diabetes (T2D) has great potential but may be insufficiently efficacious and carries risks of hypoglycaemia and ketosis. We designed the first Phase 3 clinical trial to assess the efficacy and safety of adding a Glucagon\u2010Like Peptide 1 receptor agonist (GLP\u20101RA) and a Sodium\u2010Glucose Co\u2010transporter (SGLT2) Inhibitor to insulin therapy in overweight and obese adults with T1D and glycaemia above target (HbA1c 7.5%\u201311.0% inclusive) (NCT03899402).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>In Period 1, participants are randomized 2:1 (open label) for 26\u2009weeks to semaglutide and insulin (uptitrated to 1.0\u2009mg weekly) or standard insulin therapy. In Period 2, those randomized to semaglutide and insulin in Period 1 are further randomized (double\u2010blind) for 26\u2009weeks to dapagliflozin (10\u2009mg daily) or placebo, in addition to semaglutide. The primary objective is to compare change in HbA1c on \u2018triple therapy\u2019 (dapagliflozin, semaglutide and insulin) with \u2018dual therapy\u2019 (placebo, semaglutide and insulin). Secondary objectives include comparisons of triple therapy with standard insulin therapy and dual therapy (semaglutide and insulin) with standard insulin therapy. Safety outcomes include hypoglycaemia and ketosis. A sample size recalculation during the trial based on analysis of masked data revised the original recruitment target from 114 to 82 participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The TTT1 trial will provide clinically useful information on combination adjunct therapy in the treatment of T1D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71076","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:30:52Z","timestamp":1784529052000},"page":"8812-8824","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Insulin, Semaglutide and Dapagliflozin in Adults With Type 1 Diabetes: Design and Methods of Triple Therapy for Type 1 Diabetes (\n                    <scp>TTT1<\/scp>\n                    )\u2014An International Phase 3 Clinical Trial"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3506-359X","authenticated-orcid":false,"given":"Joseph G.","family":"Timmons","sequence":"first","affiliation":[{"name":"School of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6333-6033","authenticated-orcid":false,"given":"Husam","family":"Ghanim","sequence":"additional","affiliation":[{"name":"State University of New York at Buffalo  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G.","family":"Boyle","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences University of Glasgow  Glasgow 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