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

J. Jordan*, R. Stinkens, T. Jax, S. Engeli, E. E. Blaak, M. May, B. Havekes, C. Schindler, D. Albrecht, P. Pal, T. Heise, G. H. Goossens, T. H. Langenickel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Natriuretic peptide (NP) deficiency and sustained renin-angiotensin systemactivation are associated with impaired oxidative metabolismand predispose to type-2 diabetes. We hypothesized that sacubitril/valsartan (LCZ696), which augments NP through neprilysin inhibition while blocking angiotensin II type-1 (AT1)-receptors, improves insulin sensitivity, lipid mobilization, and oxidation. After 8 weeks of treatment of obese patients with hypertension, sacubitril/valsartan 400mg 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 ametabolic benefit in the study population and supports the relevance of neprilysin inhibition along with AT1-receptor blockade in the regulation of human glucose and lipid metabolism.

Original languageEnglish
Pages (from-to)254-263
Number of pages10
JournalClinical Pharmacology & Therapeutics
Issue number2
Publication statusPublished - Feb 2017


  • LCZ696
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