{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T19:24:31Z","timestamp":1784921071292,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004836","name":"Danmarks Frie Forskningsfond","doi-asserted-by":"publisher","award":["1052\u201000003B"],"award-info":[{"award-number":["1052\u201000003B"]}],"id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018940","name":"Diabetesforeningen","doi-asserted-by":"publisher","award":["Nicolai J. Wewer Albrechtsen"],"award-info":[{"award-number":["Nicolai J. Wewer Albrechtsen"]}],"id":[{"id":"10.13039\/501100018940","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001648","name":"European Foundation for the Study of Diabetes","doi-asserted-by":"publisher","award":["NNF21SA0072746"],"award-info":[{"award-number":["NNF21SA0072746"]}],"id":[{"id":"10.13039\/501100001648","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007405","name":"Hjerteforeningen","doi-asserted-by":"publisher","award":["20\u2010R141\u2010A9782\u201022172"],"award-info":[{"award-number":["20\u2010R141\u2010A9782\u201022172"]}],"id":[{"id":"10.13039\/100007405","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF14CC0001"],"award-info":[{"award-number":["NNF14CC0001"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF18OC0032330"],"award-info":[{"award-number":["NNF18OC0032330"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF19OC0055001"],"award-info":[{"award-number":["NNF19OC0055001"]}],"id":[{"id":"10.13039\/501100009708","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":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Sacubitril\/valsartan is a neprilysin\u2010inhibitor\/angiotensin II receptor blocker used for the treatment of heart failure. Recently, a post\u2010hoc analysis of a 3\u2010year randomized controlled trial showed improved glycaemic control with sacubitril\/valsartan in patients with heart failure and type 2 diabetes. We previously reported that sacubitril\/valsartan combined with a dipeptidyl peptidase\u20104 inhibitor increases active glucagon\u2010like peptide\u20101 (GLP\u20101) in healthy individuals. We now hypothesized that administration of sacubitril\/valsartan with or without a dipeptidyl peptidase\u20104 inhibitor would lower postprandial glucose concentrations (primary outcome) in patients with type 2 diabetes via increased active GLP\u20101.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a crossover trial in 12 patients with obesity and type 2 diabetes. A mixed meal was ingested following five respective interventions: (a) a single dose of sacubitril\/valsartan; (b) sitagliptin; (c) sacubitril\/valsartan\u2009+\u2009sitagliptin; (d) control (no treatment); and (e) valsartan alone. Glucose, gut and pancreatic hormone responses were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Postprandial plasma glucose increased by 57% (incremental area under the curve 0\u2010240\u2009min) (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.0003) and increased peak plasma glucose by 1.7\u2009mM (95% CI: 0.6\u20102.9) (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.003) after sacubitril\/valsartan compared with control, whereas postprandial glucose levels did not change significantly after sacubitril\/valsartan\u2009+\u2009sitagliptin. Glucagon, GLP\u20101 and C\u2010peptide concentrations increased after sacubitril\/valsartan, but insulin and glucose\u2010dependent insulinotropic polypeptide did not change.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The glucose\u2010lowering effects of long\u2010term sacubitril\/valsartan treatment reported in patients with heart failure and type 2 diabetes may not depend on changes in entero\u2010pancreatic hormones. Neprilysin inhibition results in hyperglucagonaemia and this may explain the worsen glucose tolerance observed in this study.<\/jats:p>\n                    <jats:p>ClinicalTrials.gov (NCT03893526).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14789","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T01:04:37Z","timestamp":1654736677000},"page":"2017-2026","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Acute effects on glucose tolerance by neprilysin inhibition in patients with type 2 diabetes"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4230-5753","authenticated-orcid":false,"given":"Nicolai J.","family":"Wewer Albrechtsen","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Rigshospitalet University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"NNF Center for Protein Research, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Clinical Biochemistry, Bispebjerg and Frederiksberg Hospital University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Copenhagen University Hospital Hvidovre  Hvidovre Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoffer","family":"Martinussen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Copenhagen University Hospital Hvidovre  Hvidovre Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise L.","family":"Gluud","sequence":"additional","affiliation":[{"name":"Gastrounit, Copenhagen University Hospital Hvidovre  Hvidovre Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias B.","family":"Rashu","sequence":"additional","affiliation":[{"name":"Gastrounit, Copenhagen University Hospital Hvidovre  Hvidovre Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3861-8469","authenticated-orcid":false,"given":"Michael M.","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Rigshospitalet University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Plomgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Rigshospitalet University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens P.","family":"Goetze","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Rigshospitalet University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha","family":"Kjeldsen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"NNF Center for Protein Research, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasse Holst","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Rigshospitalet University of Copenhagen  Copenhagen Denmark"},{"name":"Copenhagen Center for Glycomics, Departments of Cellular and 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