{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:20:38Z","timestamp":1790371238082,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,7,7]],"date-time":"2019-07-07T00:00:00Z","timestamp":1562457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"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":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Glucagon\u2010like peptide\u20101 receptor agonist (GLP\u20101RA) and insulin combination therapy is an effective treatment option for type 2 diabetes, but long\u2010term data are lacking. The aim was to assess the long\u2010term efficacy of the GLP\u20101RA liraglutide in subgroups by insulin use in the LEADER trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>LEADER assessed cardiovascular (CV) safety and efficacy of liraglutide (1.8 mg) versus placebo (plus standard of care therapy) in 9340 patients with type 2 diabetes and high risk of CV disease, for up to 5 years. We analyzed CV events, metabolic parameters and hypoglycaemia post hoc in three subgroups by baseline insulin use (basal\u2010only insulin, other insulin or no insulin). Insulin was a non\u2010random treatment allocation as part of standard of care therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At baseline, 5171 (55%) patients were not receiving insulin, 3159 (34%) were receiving basal\u2010only insulin and 1010 (11%) other insulins. Insulin users had a longer diabetes duration and slightly worse glycaemic control (HbA1c) than the no\u2010insulin subgroup. Liraglutide reduced HbA1c and weight versus placebo in all three subgroups (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;\u2009.001), and severe hypoglycaemia rate in the basal\u2010only insulin subgroup. The need for insulin was less with liraglutide. CV risk reduction with liraglutide was similar to the main trial results in the basal\u2010only and no\u2010insulin subgroups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients on insulin, liraglutide improved glycaemic control, weight and need for insulin versus placebo, for at least 36\u2009months with no increased risk of severe hypoglycaemia, while maintaining CV safety\/efficacy, supporting the combination of liraglutide and insulin for management of type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13826","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T01:59:11Z","timestamp":1562551151000},"page":"2450-2458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Long\u2010term efficacy and safety of combined insulin and glucagon\u2010like peptide\u20101 therapy: Evidence from the LEADER trial"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0322-1653","authenticated-orcid":false,"given":"Cees J.","family":"Tack","sequence":"first","affiliation":[{"name":"Radboud University Medical Center Nijmegen  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Jacob","sequence":"additional","affiliation":[{"name":"Praxis f\u00fcr Pr\u00e4vention und Therapie Kardio Metabolisches Institut  Villingen\u2010Schwenningen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus","family":"Desouza","sequence":"additional","affiliation":[{"name":"Veterans Affairs Medical Center  Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8519-4964","authenticated-orcid":false,"given":"Stephen C.","family":"Bain","sequence":"additional","affiliation":[{"name":"Swansea University Medical School  Swansea UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Buse","sequence":"additional","affiliation":[{"name":"University of North Carolina School of Medicine  Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5749-6954","authenticated-orcid":false,"given":"Michael A.","family":"Nauck","sequence":"additional","affiliation":[{"name":"Diabetes Center Bochum\u2010Hattingen St Josef Hospital (Ruhr\u2010Universit\u00e4t Bochum)  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Petrie","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil R.","family":"Poulter","sequence":"additional","affiliation":[{"name":"International Centre for Circulatory Health Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Pratley","sequence":"additional","affiliation":[{"name":"AdventHealth Translational Research Institute  Orlando Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen Vanya B. K.","family":"Stegmann","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidrun","family":"Bosch\u2010Traberg","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Startseva","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0041-1876","authenticated-orcid":false,"given":"Bernard","family":"Zinman","sequence":"additional","affiliation":[{"name":"Lunenfeld\u2013Tanenbaum Research Institute, Mt. 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