{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T03:58:57Z","timestamp":1784001537584,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T00:00:00Z","timestamp":1685318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005302","name":"Alexander S. Onassis Public Benefit Foundation","doi-asserted-by":"publisher","award":["G ZO 011\u20101\/ 2018\u20102019"],"award-info":[{"award-number":["G ZO 011\u20101\/ 2018\u20102019"]}],"id":[{"id":"10.13039\/501100005302","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K24DK081913"],"award-info":[{"award-number":["K24DK081913"]}],"id":[{"id":"10.13039\/100000062","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":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate the changes of circulating levels of all proglucagon\u2010derived peptides (PGDPs) in individuals with overweight or obesity receiving liraglutide (3\u2009mg) or naltrexone\/bupropion (32\/360\u2009mg), and to explore the association between induced changes in postprandial PGDP levels and body composition, as well as metabolic variables, after 3 and 6\u2009months on treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Seventeen patients with obesity or with overweight and co\u2010morbidities, but without diabetes, were assigned to receive once\u2010daily oral naltrexone\/bupropion 32\/360\u2009mg (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098) or once\u2010daily subcutaneous liraglutide 3\u2009mg (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099). Participants were assessed before treatment initiation and after 3 and 6\u2009months on treatment. At the baseline and 3\u2010month visits, participants underwent a 3\u2010hour mixed meal tolerance test to measure fasting and postprandial levels of PGDPs, C\u2010peptide, hunger and satiety. Clinical and biochemical indices of metabolic function, magnetic resonance\u2010assessed liver steatosis and ultrasound\u2010assessed liver stiffness were measured at each visit.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both medications improved body weight and composition, carbohydrate and lipid metabolism, and liver fat and function. Naltrexone\/bupropion produced a weight\u2010independent increase in the levels of proglucagon (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.001) and decreases in glucagon\u2010like peptide\u20102 (GLP\u20102), glucagon and the major proglucagon fragment (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009\u2264\u2009.01), whereas liraglutide markedly upregulated total glucagon\u2010like peptide\u20101 (GLP\u20101) levels in a weight\u2010independent manner (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.04), and similarly downregulated the major proglucagon fragment, GLP\u20102 and glucagon (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.01). PGDP levels at the 3\u2010month visit were positively and independently correlated with improvements in fat mass, glycaemia, lipaemia and liver function, and negatively with reductions in fat\u2010free mass, at both the 3\u2010 and 6\u2010month visits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PGDP levels in response to liraglutide and naltrexone\/bupropion are associated with improvements in metabolism. Our study provides support for the administration of the downregulated members of the PGDP family as replacement therapy (e.g. glucagon), in addition to the medications currently in use that induced their downregulation (e.g. GLP\u20101), and future studies should explore whether the addition of other PGDPs (e.g. GLP\u20102) could offer additional benefits.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15141","type":"journal-article","created":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T07:35:10Z","timestamp":1685345710000},"page":"2561-2574","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Circulating levels of proglucagon\u2010derived peptides are differentially regulated by the glucagon\u2010like peptide\u20101 agonist liraglutide and the centrally acting naltrexone\/bupropion and can predict future weight loss and metabolic improvements: A 6\u2010month long interventional study"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5512-2388","authenticated-orcid":false,"given":"Konstantinos","family":"Stefanakis","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine Boston VA Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School  Boston Massachusetts USA"},{"name":"First Department of Propaedeutic Internal Medicine, Laiko General Hospital National and Kapodistrian University of Athens School of Medicine  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5491-2545","authenticated-orcid":false,"given":"Alexander","family":"Kokkinos","sequence":"additional","affiliation":[{"name":"First Department of Propaedeutic Internal Medicine, Laiko General Hospital National and Kapodistrian University of Athens School of Medicine  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5502-565X","authenticated-orcid":false,"given":"Georgia","family":"Argyrakopoulou","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Unit Athens Medical Center  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia K.","family":"Konstantinidou","sequence":"additional","affiliation":[{"name":"First Department of Propaedeutic Internal Medicine, Laiko General Hospital National and Kapodistrian University of Athens School of Medicine  Athens Greece"},{"name":"Diabetes and Obesity Unit Athens Medical Center  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stamatia","family":"Simati","sequence":"additional","affiliation":[{"name":"First Department of Propaedeutic Internal Medicine, Laiko General Hospital National and Kapodistrian University of Athens School of Medicine  Athens 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