دورية أكاديمية
Acute effects on glucose tolerance by neprilysin inhibition in patients with type 2 diabetes.
العنوان: | Acute effects on glucose tolerance by neprilysin inhibition in patients with type 2 diabetes. |
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المؤلفون: | Wewer Albrechtsen NJ; Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Biochemistry, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark., Møller A; Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark., Martinussen C; Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark., Gluud LL; Gastrounit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark., Rashu EB; Gastrounit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark., Richter MM; Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Plomgaard P; Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Goetze JP; Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Kjeldsen S; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Hansen LH; Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.; Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark., Gustafsson F; Department of Cardiology, Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Deacon CF; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; School of Biomedical Sciences, Ulster University, Coleraine, UK., Holst JJ; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Madsbad S; Department of Clinical Biochemistry, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark., Bojsen-Møller KN; Department of Clinical Biochemistry, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark. |
المصدر: | Diabetes, obesity & metabolism [Diabetes Obes Metab] 2022 Oct; Vol. 24 (10), pp. 2017-2026. Date of Electronic Publication: 2022 Jul 21. |
نوع المنشور: | Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 100883645 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1463-1326 (Electronic) Linking ISSN: 14628902 NLM ISO Abbreviation: Diabetes Obes Metab Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Oxford : Wiley-Blackwell, c1999- |
مواضيع طبية MeSH: | Aminobutyrates*/therapeutic use , Angiotensin Receptor Antagonists*/therapeutic use , Biphenyl Compounds*/therapeutic use , Blood Glucose*/analysis , Blood Glucose*/drug effects , Diabetes Mellitus, Type 2*/complications , Diabetes Mellitus, Type 2*/drug therapy , Heart Failure*/complications , Heart Failure*/drug therapy , Hypoglycemic Agents*/therapeutic use , Neprilysin*/antagonists & inhibitors , Valsartan*/therapeutic use, Aged ; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use ; Drug Combinations ; Glucagon-Like Peptide 1/blood ; Glucose Tolerance Test ; Humans ; Male ; Middle Aged ; Sitagliptin Phosphate/therapeutic use ; Tetrazoles/therapeutic use |
مستخلص: | Aims: Sacubitril/valsartan is a neprilysin-inhibitor/angiotensin II receptor blocker used for the treatment of heart failure. Recently, a post-hoc analysis of a 3-year 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-4 inhibitor increases active glucagon-like peptide-1 (GLP-1) in healthy individuals. We now hypothesized that administration of sacubitril/valsartan with or without a dipeptidyl peptidase-4 inhibitor would lower postprandial glucose concentrations (primary outcome) in patients with type 2 diabetes via increased active GLP-1. Methods: 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 + sitagliptin; (d) control (no treatment); and (e) valsartan alone. Glucose, gut and pancreatic hormone responses were measured. Results: Postprandial plasma glucose increased by 57% (incremental area under the curve 0-240 min) (p = .0003) and increased peak plasma glucose by 1.7 mM (95% CI: 0.6-2.9) (p = .003) after sacubitril/valsartan compared with control, whereas postprandial glucose levels did not change significantly after sacubitril/valsartan + sitagliptin. Glucagon, GLP-1 and C-peptide concentrations increased after sacubitril/valsartan, but insulin and glucose-dependent insulinotropic polypeptide did not change. Conclusions: The glucose-lowering effects of long-term sacubitril/valsartan treatment reported in patients with heart failure and type 2 diabetes may not depend on changes in entero-pancreatic hormones. Neprilysin inhibition results in hyperglucagonaemia and this may explain the worsen glucose tolerance observed in this study. Clinicaltrials: gov (NCT03893526). (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.) |
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فهرسة مساهمة: | Keywords: GLP-1; clinical trial; drug mechanism; glucagon; glycaemic control |
سلسلة جزيئية: | ClinicalTrials.gov NCT03893526 |
المشرفين على المادة: | 0 (Aminobutyrates) 0 (Angiotensin Receptor Antagonists) 0 (Biphenyl Compounds) 0 (Blood Glucose) 0 (Dipeptidyl-Peptidase IV Inhibitors) 0 (Drug Combinations) 0 (Hypoglycemic Agents) 0 (Tetrazoles) 17ERJ0MKGI (sacubitril) 80M03YXJ7I (Valsartan) 89750-14-1 (Glucagon-Like Peptide 1) EC 3.4.24.11 (Neprilysin) TS63EW8X6F (Sitagliptin Phosphate) |
تواريخ الأحداث: | Date Created: 20220609 Date Completed: 20220908 Latest Revision: 20221015 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC9545540 |
DOI: | 10.1111/dom.14789 |
PMID: | 35676803 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1463-1326 |
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DOI: | 10.1111/dom.14789 |