The Effects of Neprilysin on Glucagon-like Peptide-1

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

Detailed Description
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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

Official Title
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The Effects of Neprilysin on Glucagon-like Peptide-1

Conditions
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Diabetes, Heart Failure

Intervention / Treatment
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* Drug: Entresto
* Drug: Sitagliptin 100mg
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The participants are on 4 study days with wash out period of minimum 2 weeks randomized to 4 intervention arms
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>No treatment. Participants are subjected to a standardized meal | Drug: Placebos<br>* No treatment<br>* Other names: placebo;|
| Active Comparator: Entrestro as single dose<br>194 mg sacubitril / 206 mg valstartan (entresto) as one single dose followed by a standardized meal | Drug: Entresto<br>* Single dose administration of Entrestro 194 mg sacubitril / 206 mg valstartan<br>* Other names: Neprilysin inhibibitor;|
| Active Comparator: Sitagliptin as single dose<br>200mg sitagliptin (100mg the night before and 100mg on the study day) as one single dose followed by a standardized meal | Drug: Sitagliptin 100mg<br>* 2 x 100mg sitagliptin as single dose.<br>* Other names: DPP-4 inhibitor;|
| Active Comparator: Entrestro + sitagliptin as single dose<br>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 | Drug: Entresto<br>* Single dose administration of Entrestro 194 mg sacubitril / 206 mg valstartan<br>* Other names: Neprilysin inhibibitor;Drug: Sitagliptin 100mg<br>* 2 x 100mg sitagliptin as single dose.<br>* Other names: DPP-4 inhibitor;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GLP-1, Neprilysin, DPP-4