Effect of Neprilysin on Glucagon-Like Peptide-1 in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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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 with type 2 diabetes 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 placebo, to patients with type 2 diabetes during a standardized meal and measured plasma concentrations of GLP-1

Official Title
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The Effect of Neprilysin on Plasma Concentrations of Glucagon-Like Peptide-1 in Patients With Type 2 Diabetes

Conditions
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Type2 Diabetes

Intervention / Treatment
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* Drug: Entresto
* Drug: Sitagliptin
* Drug: Valsartan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 Diabetes Oral Antidiabetics Medicine Only Body Mass Index of 25-35 Type 2 Diabetes 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: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants are subjected to a standardized meal | Drug: Placebo<br>* placebo day<br>|
| Active Comparator: Entrestro<br>194 mg sacubitril / 206 mg valstartan (entresto) as one single dose followed by a standardized meal | Drug: Entresto<br>* Single dose administration of entresto<br>|
| Active Comparator: Sitagliptin<br>200mg sitagliptin (100mg the night before and 100mg on the study day) as one single dose followed by a standardized meal | Drug: Sitagliptin<br>* Single dose administration of sitagliptin<br>|
| Active Comparator: Entrestro + sitagliptin<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 entresto<br>Drug: Sitagliptin<br>* Single dose administration of sitagliptin<br>|
| Active Comparator: Valsartan<br>206mg valsartan as one single dose followed by a standardized meal | Drug: Valsartan<br>* single doses administration of valsartan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Glucose | Plasma Concentrations of glucose | 3 hours after treatment ( during the subsequent standardized meal) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentrations of GLP-1 |  | 3 hours after treatment ( during the subsequent standardized meal) | 
| Plasma Concentrations of GIP |  | 3 hours after treatment ( during the subsequent standardized meal) | 
| Plasma Concentrations of Glucagon |  | 3 hours after treatment ( during the subsequent standardized meal) | 
| Plasma Concentrations of Insulin |  | 3 hours after treatment ( during the subsequent standardized meal) | 
| Plasma Concentrations of C-Peptide |  | 3 hours after treatment ( during the subsequent standardized meal) | 
| Plasma Concentrations of Amino Acids |  | 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, Diabetes