{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:02:33Z","timestamp":1779879753209,"version":"3.53.1"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,11,19]],"date-time":"2014-11-19T00:00:00Z","timestamp":1416355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate glucose\u2010lowering treatment strategies with linagliptin and metformin in people with newly diagnosed type 2 diabetes and marked hyperglycaemia, a prevalent population for which few dedicated studies of oral antidiabetes drugs have been conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 316 patients, with type 2 diabetes diagnosed for \u226412\u2009months and with glycated haemoglobin (\n                      <jats:styled-content style=\"fixed-case\">HbA1c<\/jats:styled-content>\n                      ) concentration in the range 8.5\u201312.0%, were randomized 1:1 to double\u2010blind, free\u2010combination treatment with linagliptin 5\u2009mg once daily and metformin twice daily (uptitrated to 2000\u2009mg\/day maximum) or to linagliptin monotherapy. The primary endpoint was change in\n                      <jats:styled-content style=\"fixed-case\">HbA1c<\/jats:styled-content>\n                      concentration from baseline at week 24 (per\u2010protocol completers' cohort: n\u2009=\u2009245).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The mean (standard deviation) age and\n                      <jats:styled-content style=\"fixed-case\">HbA1c<\/jats:styled-content>\n                      at baseline were 48.8 (11.0) years and 9.8 (1.1)%, respectively. At week 24, the mean\u2009\u00b1\u2009standard error (s.e.)\n                      <jats:styled-content style=\"fixed-case\">HbA1c<\/jats:styled-content>\n                      decreased from baseline by \u20132.8\u2009\u00b1\u20090.1% with linagliptin\/metformin and \u20132.0\u2009\u00b1\u20090.1% with linagliptin; a treatment difference of \u20130.8% (95% confidence interval \u20131.1 to \u20130.5; p &lt;0.0001). Similar results were observed in a sensitivity analysis based on intent\u2010to\u2010treat principles: adjusted mean\u2009\u00b1\u2009s.e. changes in\n                      <jats:styled-content style=\"fixed-case\">HbA1c<\/jats:styled-content>\n                      of \u20132.7\u2009\u00b1\u20090.1% and \u20131.8\u2009\u00b1\u20090.1%, respectively; treatment difference of \u20130.9% (95%\n                      <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\n                      \u20131.3 to \u20130.6; p &lt;0.0001). A treatment response of\n                      <jats:styled-content style=\"fixed-case\">HbA1c<\/jats:styled-content>\n                      &lt;7.0% was achieved by 61 and 40% of patients in the linagliptin\/metformin and linagliptin groups, respectively. Few patients experienced drug\u2010related adverse events (8.8 and 5.7% of patients in the linagliptin\/metformin and linagliptin groups, respectively). Hypoglycaemia occurred in 1.9 and 3.2% of patients in the linagliptin\/metformin and linagliptin groups, respectively (no severe episodes). Body weight decreased significantly with the combination therapy (\u20131.3\u2009kg between\u2010group difference; p =0.0033).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Linagliptin in initial combination with metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia, an understudied group, elicited significant improvements in glycaemic control with a low incidence of hypoglycaemia, weight gain or other adverse effects. These results support early combination treatment strategies and suggest that newly diagnosed patients with marked hyperglycaemia may be effectively managed with oral, non\u2010insulin therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.12399","type":"journal-article","created":{"date-parts":[[2014,10,8]],"date-time":"2014-10-08T23:03:44Z","timestamp":1412809424000},"page":"136-144","source":"Crossref","is-referenced-by-count":22,"title":["Initial combination of linagliptin and metformin compared with linagliptin monotherapy in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia: a randomized, double\u2010blind, active\u2010controlled, parallel group, multinational clinical trial"],"prefix":"10.1111","volume":"17","author":[{"given":"S. A.","family":"Ross","sequence":"first","affiliation":[{"name":"University of Calgary LMC Endocrinology Centres  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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