The Effects of Neprilysin on Glucagon-like Peptide-1

Overview

In the current study we wish to investigate the effects on glucagon-like peptide-1 (GLP-1) of a neprilysin inhibitor

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 1, 2019

Detailed Description

Glucagon-like peptide-1(GLP-1) is secreted during a meal and increases glucose induced insulin secretion. The enzyme dipeptidyl peptidase 4(DPP-4) cleaves intact GLP-1 within minutes and DPP-4 inhibitors are therefore used for treatment of diabetic hyperglycemia. A few animal studies have implicated the enzyme neutral endopeptidase 24.11 (24.11) in the degradation of GLP-1 but if this is the case in humans is unknown. We therefore administered a NEP inhibitor, 194mg sacubitril, a DPP-4 inhibitor (sitagliptin 100mg the night before and 100mg 2 hours before), both, or place, to nine healthy men during a standardized meal and measured plasma concentrations of GLP-1

Interventions

  • Drug: Entresto
    • Single dose administration of Entrestro 194 mg sacubitril / 206 mg valstartan
  • Drug: Sitagliptin 100mg
    • 2 x 100mg sitagliptin as single dose.
  • Drug: Placebos
    • No treatment

Arms, Groups and Cohorts

  • Placebo Comparator: Placebo
    • No treatment. Participants are subjected to a standardized meal
  • Active Comparator: Entrestro as single dose
    • 194 mg sacubitril / 206 mg valstartan (entresto) as one single dose followed by a standardized meal
  • Active Comparator: Sitagliptin as single dose
    • 200mg sitagliptin (100mg the night before and 100mg on the study day) as one single dose followed by a standardized meal
  • Active Comparator: Entrestro + sitagliptin as single dose
    • 194 mg sacubitril / 206 mg valstartan (entresto) + 200mg sitagliptin (100mg the night before and 100mg on the study day) as one single dose followed by a standardized meal

Clinical Trial Outcome Measures

Primary Measures

  • GLP-1
    • Time Frame: 3 hours after treatment ( during the subsequent standardized meal)
    • changes in plasma GLP-1 using immunological methods: intact and total GLP-1

Secondary Measures

  • C-peptide
    • Time Frame: 3 hours after treatment ( during the subsequent standardized meal)
    • changes in C-peptide using immunological methods
  • Glucagon
    • Time Frame: 3 hours after treatment ( during the subsequent standardized meal)
    • Changes in Plasma glucagon concentrations using different analytical methodologies

Participating in This Clinical Trial

Inclusion Criteria

  • men – body mass index between 20-25 Exclusion Criteria:

  • acute diseases within the two weeks – chronic diseases – smoker – alcoholism, drug addiction or recent weight loss – blood donation within the last 3 months

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: 30 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Nicolai Jacob Wewer Albrechtsen
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Nicolai Jacob Wewer Albrechtsen, Junior Consultant – University of Copenhagen

Citations Reporting on Results

Wewer Albrechtsen NJ, Mark PD, Terzic D, Hansen LH, Andersen UO, Hartmann B, Carr RD, Gustafsson F, Deacon CF, Holst JJ, Goetze JP, Plomgaard P. Sacubitril/Valsartan Augments Postprandial Plasma Concentrations of Active GLP-1 When Combined With Sitagliptin in Men. J Clin Endocrinol Metab. 2019 Sep 1;104(9):3868-3876. doi: 10.1210/jc.2019-00515.

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