Acute effects on glucose tolerance by neprilysin inhibition in patients with type 2 diabetes
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AIMS: Sacubitril/valsartan is a neprilysin-inhibitor/angiotensin II receptor blocker used for treatment of heart failure. Recently, a posthoc analysis of a 3-year RCT showed improved glycemic control with sacubitril/valsartan in patients with heart failure and type 2 diabetes. We previously reported that sacubitril/valsartan combined with a DPP-4 inhibitor increases active GLP-1 in healthy individuals. We now hypothesized that administration of sacubitril/valsartan with or without a DPP-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: 1) a single dose of sacubitril/valsartan, 2) sitagliptin, 3) sacubitril/valsartan + sitagliptin, 4) control (no treatment), and 5) valsartan alone. Glucose, gut and pancreatic hormone responses were measured.
RESULTS: Postprandial plasma glucose increased by 57% (iAUC 0-240min ) (P=0.0003) and increased peak plasma glucose by 1.7mM [95% CI: 0.6 - 2.9] (P=0.003) after sacubitril/valsartan compared to 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 GIP 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 hyperglucagonemia and this may explain the worsen glucose tolerance observed in this study. This article is protected by copyright. All rights reserved.
Originalsprog | Engelsk |
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Tidsskrift | Diabetes, Obesity and Metabolism |
Vol/bind | 24 |
Udgave nummer | 10 |
Sider (fra-til) | 2017-2026 |
Antal sider | 10 |
ISSN | 1462-8902 |
DOI | |
Status | Udgivet - 2022 |
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This article is protected by copyright. All rights reserved.
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