{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:38:49Z","timestamp":1792471129177,"version":"4.5.0"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","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>\n                      Type 2 diabetes (T2D) management with basal insulin can lead to hypoglycaemia and weight gain. SUSTAIN OPTIMIZE compared once\u2010weekly semaglutide 2.0\u2009mg as add\u2010on to dose\u2010reduced insulin glargine (Sema+IGlar\n                      <jats:sub>reduced<\/jats:sub>\n                      ) versus dose\u2010titrated IGlar (IGlar\n                      <jats:sub>titrated<\/jats:sub>\n                      ) on glycated haemoglobin (HbA\n                      <jats:sub>1c<\/jats:sub>\n                      ), body weight (BW), daily insulin dose, and participant satisfaction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      SUSTAIN OPTIMIZE was a 40\u2010week, phase 3b, open\u2010label, randomised study. Adults with T2D, overweight (body mass index \u2265\u200925\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ), and treatment with basal insulin \u2264\u200940\u2009units\/day were randomised 1:1 into Sema+IGlar\n                      <jats:sub>reduced<\/jats:sub>\n                      or IGlar\n                      <jats:sub>titrated<\/jats:sub>\n                      . The primary endpoint was change in HbA\n                      <jats:sub>1c<\/jats:sub>\n                      using a non\u2010inferiority approach. Secondary endpoints assessed superiority of Sema+IGlar\n                      <jats:sub>reduced<\/jats:sub>\n                      versus IGlar\n                      <jats:sub>titrated<\/jats:sub>\n                      in reducing HbA\n                      <jats:sub>1c<\/jats:sub>\n                      , BW, daily insulin dose, and improving Diabetes Treatment Satisfaction Questionnaire change version (DTSQc) scores.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 573 participants were randomised. Sema+IGlar\n                      <jats:sub>reduced<\/jats:sub>\n                      achieved both non\u2010inferiority and superiority versus IGlar\n                      <jats:sub>titrated<\/jats:sub>\n                      in HbA\n                      <jats:sub>1c<\/jats:sub>\n                      reduction (estimated treatment difference [ETD]: \u22120.74%; 95% confidence interval [CI\n                      <jats:sub>95<\/jats:sub>\n                      ]: \u22120.90, \u22120.59) and superiority in BW change (ETD: \u22128.5\u2009kg; CI\n                      <jats:sub>95<\/jats:sub>\n                      : \u22129.5, \u22127.4), relative daily insulin dose change (ETD: \u2212121.9%; CI\n                      <jats:sub>95<\/jats:sub>\n                      : \u2212143.1, \u2212100.6), and DTSQc scores (ETD: 2.6; CI\n                      <jats:sub>95<\/jats:sub>\n                      : 1.6, 3.5) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001 for all endpoints). No new safety concerns were identified. Severe hypoglycaemia was reduced (rate ratio: 0.45; CI\n                      <jats:sub>95<\/jats:sub>\n                      : 0.23, 0.87;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02), while gastrointestinal events were higher for Sema+IGlar\n                      <jats:sub>reduced<\/jats:sub>\n                      (310 vs. 32 events).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Once\u2010weekly subcutaneous semaglutide 2.0\u2009mg as add\u2010on to dose\u2010reduced IGlar achieved superior reductions in HbA\n                      <jats:sub>1c<\/jats:sub>\n                      , BW, and daily insulin dose in people with T2D and overweight, while reducing their risk for severe hypoglycaemia compared to dose\u2010titrated IGlar alone.\n                    <\/jats:p>\n          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