Trial reportDiabetes, obesity & metabolism2022
Acute effects on glucose tolerance by neprilysin inhibition in patients with type 2 diabetes.
Trial report in Diabetes, obesity & metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03893526 (The Effect of Neprilysin on Plasma Concentrations of Glucagon-Like Peptide-1 in Patients With Type 2 Diabetes), which is not on this map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Effect of Neprilysin on Plasma Concentrations of Glucagon-Like Peptide-1 in Patients With Type 2 Diabetes
Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Acute effects on glucose tolerance by neprilysin inhibition in patients with type 2 diabetes.Diabetes, obesity & metabolism · 2022Trial
- Pseudo-nephropathy and hyper-excretion of urinary C-peptide: an overlooked adverse effect of an angiotensin receptor-neprilysin inhibitor (ARNI).Diabetology international · 2024Article
- Gut-specific Neprilysin Deletion Protects Against Fat-induced Insulin Secretory Dysfunction in Male Mice.Endocrinology · 2024Article
- Update on clinical and experimental management of diabetic cardiomyopathy: addressing current and future therapy.Frontiers in endocrinology · 2024Review
- Article
- Article
- Impact of the angiotensin receptor-neprilysin inhibitor in clinical diabetes management: Potential benefits and pitfalls.Journal of diabetes investigation · 2023Article
- Effects of neprilysin and neprilysin inhibitors on glucose homeostasis: Controversial points and a promising arena.Journal of diabetes · 2023Review
- Acute Inhibition of Intestinal Neprilysin Enhances Insulin Secretion via GLP-1 Receptor Signaling in Male Mice.Endocrinology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsSacubitril/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.
methodsWe 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.
resultsPostprandial 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.
conclusionsThe 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).
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