The effects of angiotensin receptor neprilysin inhibition by sacubitril/valsartan on adipose tissue transcriptome and protein expression in obese hypertensive patients.

Increased activation of the renin-angiotensin system is involved in the onset and progression of cardiometabolic diseases, while natriuretic peptides (NP) may exert protective effects. We have recently demonstrated that sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, which blocks the angiotensin II type-1 receptor and augments natriuretic peptide levels, improved peripheral insulin sensitivity in obese hypertensive patients. Here, we investigated the effects of sacubitril/valsartan (400 mg QD) treatment for 8 weeks on the abdominal subcutaneous adipose tissue (AT) phenotype compared to the metabolically neutral comparator amlodipine (10 mg QD) in 70 obese hypertensive patients.

Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension.

Unlabelled: Sacubitril/valsartan (LCZ696), a novel angiotensin receptor-neprilysin inhibitor, was recently approved for the treatment of heart failure with reduced ejection fraction. Neprilysin degrades several peptides that modulate lipid metabolism, including natriuretic peptides. In this study, we investigated the effects of 8 weeks' treatment with sacubitril/valsartan on whole-body and adipose tissue lipolysis and lipid oxidation during defined physical exercise compared with the metabolically neutral comparator amlodipine.

A randomised, active- and placebo-controlled, three-period crossover trial to investigate short-term effects of the dipeptidyl peptidase-4 inhibitor linagliptin on macro- and microvascular endothelial function in type 2 diabetes.

Background: Studies of dipeptidyl peptidase (DPP)-4 inhibitors report heterogeneous effects on endothelial function in patients with type 2 diabetes (T2D). This study assessed the effects of the DPP-4 inhibitor linagliptin versus the sulphonylurea glimepiride and placebo on measures of macro- and microvascular endothelial function in patients with T2D who represented a primary cardiovascular disease prevention population.

Methods: This crossover study randomised T2D patients (n = 42) with glycated haemoglobin (HbA1c) ≤7.

Improved Insulin Sensitivity With Angiotensin Receptor Neprilysin Inhibition in Individuals With Obesity and Hypertension.

Natriuretic peptide (NP) deficiency and sustained renin-angiotensin system activation are associated with impaired oxidative metabolism and predispose to type-2 diabetes. We hypothesized that sacubitril/valsartan (LCZ696), which augments NP through neprilysin inhibition while blocking angiotensin II type-1 (AT )-receptors, improves insulin sensitivity, lipid mobilization, and oxidation. After 8 weeks of treatment of obese patients with hypertension, sacubitril/valsartan 400 mg q.

Pharmacokinetics and pharmacodynamics of various glucagon dosages at different blood glucose levels.

Aims: To evaluate the pharmacokinetics and pharmacodynamics of different doses of glucagon administered subcutaneously (s.c.) at different blood glucose levels.