دورية أكاديمية
أعرض في EDS

Acute effects on glucose tolerance by neprilysin inhibition in patients with type 2 diabetes.

التفاصيل البيبلوغرافية
العنوان: Acute effects on glucose tolerance by neprilysin inhibition in patients with type 2 diabetes.
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
الوصف
تدمد:1463-1326
DOI:10.1111/dom.14789