The dual inhibitor Sacubitril-valsartan ameliorate high-fat high-fructose-induced metabolic disorders in rats superiorly compared to valsartan only

J Pharm Pharmacol. 2023 Jun 5;75(6):846-858. doi: 10.1093/jpp/rgad012.

Abstract

Objectives: Sacubitril-valsartan, a recently approved treatment for heart failure, has shown some promise as a possible therapeutic option for diabetes mellitus. It is still not clear whether those beneficial effects are comparable to valsartan effects. In this work, we aimed at investigating Sacubitril-valsartan effect on metabolic changes in a model of high-fat high fructose diet-induced diabetes mellitus, in comparison to the metabolic changes induced by valsartan only.

Methods: Rats were ad libitum fed with either standard chow plus tap water for drinking (controls) or 60% beef tallow and 10% fructose drinking water (diseased) for 11 weeks. Starting in week 9, each group was subdivided into four, namely vehicle, pioglitazone, Sacubitril-valsartan and valsartan. Treatments were administered from weeks 9 to 11, while rats were maintained in their respective diet groups.

Key findings: Sacubitril-valsartan treatment significantly decreased daily food intake, body weight and epididymal white adipose weight, and normalized insulin and glycosylated haemoglobin in high-fat high fructose. Both valsartan and Sacubitril-valsartan only attenuated the elevated fasting blood glucose levels, glucose, insulin and pyruvate tolerance and increased protein kinase B phosphorylation in diseased rats.

Conclusions: Sacubitril-valsartan may be an effective modulator of diabetes mellitus-associated metabolic aberration, superiorly compared to valsartan only.

Keywords: Hb A1c; High-fat high fructose; Sacubitril-valsartan; body weight; insulin.

MeSH terms

  • Angiotensin Receptor Antagonists / pharmacology
  • Animals
  • Biphenyl Compounds / therapeutic use
  • Cattle
  • Drug Combinations
  • Heart Failure* / drug therapy
  • Insulin
  • Metabolic Diseases* / drug therapy
  • Rats
  • Tetrazoles / pharmacology
  • Tetrazoles / therapeutic use
  • Valsartan / pharmacology
  • Valsartan / therapeutic use

Substances

  • sacubitril and valsartan sodium hydrate drug combination
  • Tetrazoles
  • Angiotensin Receptor Antagonists
  • Valsartan
  • Biphenyl Compounds
  • Drug Combinations
  • Insulin