Premium
Improved Insulin Sensitivity With Angiotensin Receptor Neprilysin Inhibition in Individuals With Obesity and Hypertension
Author(s) -
Jordan J,
Stinkens R,
Jax T,
Engeli S,
Blaak EE,
May M,
Havekes B,
Schindler C,
Albrecht D,
Pal P,
Heise T,
Goossens GH,
Langenickel TH
Publication year - 2017
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.455
Subject(s) - medicine , valsartan , endocrinology , sacubitril, valsartan , neprilysin , amlodipine , sacubitril , angiotensin receptor , angiotensin ii , chemistry , receptor , blood pressure , biochemistry , enzyme
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 1 )‐receptors, improves insulin sensitivity, lipid mobilization, and oxidation. After 8 weeks of treatment of obese patients with hypertension, sacubitril/valsartan 400 mg q.d., but not amlodipine 10 mg q.d., was associated with a significant increase from baseline in the insulin sensitivity index (hyperinsulinemic‐euglycemic clamp), and tended to be higher in patients treated with sacubitril/valsartan compared to amlodipine. Abdominal adipose tissue interstitial glycerol concentrations increased with sacubitril/valsartan, but decreased with amlodipine. Whole‐body lipolysis and substrate oxidation did not change with either treatment. Results confirm that sacubitril/valsartan treatment leads to a metabolic benefit in the study population and supports the relevance of neprilysin inhibition along with AT 1 ‐receptor blockade in the regulation of human glucose and lipid metabolism.