The Effects of Neprilysin on Glucagon-like Peptide-1

Phase 4

Completed

• Conditions: Diabetes; Heart Failure
• Interventions: Drug: Entresto; Drug: Placebos; Drug: Sitagliptin 100mg

• Registration Number: NCT03717688
• Lead Sponsor: Nicolai Jacob Wewer Albrechtsen

Brief Summary

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

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

Study Timeline

• Study Start: 2018-05-17
• Study First Submitted: 2018-09-20
• Study First Submitted QC: 2018-10-23
• Study First Posted: 2018-10-24
• Primary Completion: 2019-02-01
• Study Completion: 2019-05-14
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-03
• Last Update Posted: 2019-07-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 19

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

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

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Copenhagen; 🇩🇰 Copenhagen, Denmark