Acute effects on glucose tolerance by neprilysin inhibition in patients with type 2 diabetes.
Diabetes Obes Metab
; 24(10): 2017-2026, 2022 10.
Article
en En
| MEDLINE
| ID: mdl-35676803
ABSTRACT
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 respectiveinterventions:
(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).Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Compuestos de Bifenilo
/
Glucemia
/
Neprilisina
/
Diabetes Mellitus Tipo 2
/
Antagonistas de Receptores de Angiotensina
/
Valsartán
/
Aminobutiratos
/
Insuficiencia Cardíaca
/
Hipoglucemiantes
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Aged
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Diabetes Obes Metab
Asunto de la revista:
ENDOCRINOLOGIA
/
METABOLISMO
Año:
2022
Tipo del documento:
Article
País de afiliación:
Dinamarca