The Effects of Neprilysin on Glucagon-like Peptide-1 (NEP)

Nicolai Jacob Wewer Albrechtsen

Status and phase: Completed; Phase 4

Conditions: Diabetes; Heart Failure

Treatments: Drug: Entresto; Drug: Placebos; Drug: Sitagliptin 100mg

Study type: Interventional

Funder types: Other

Identifiers

NCT03717688

NEP and GLP-1

Details and patient eligibility

About

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

Full 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

Enrollment: 19 patients

Sex: Male

Ages: 18 to 30 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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19 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

No treatment. Participants are subjected to a standardized meal

Treatment:

Drug: Placebos

Entrestro as single dose

Active Comparator group

Description:

194 mg sacubitril / 206 mg valstartan (entresto) as one single dose followed by a standardized meal

Treatment:

Drug: Entresto

Sitagliptin as single dose

Active Comparator group

Description:

200mg sitagliptin (100mg the night before and 100mg on the study day) as one single dose followed by a standardized meal

Treatment:

Drug: Sitagliptin 100mg

Entrestro + sitagliptin as single dose

Active Comparator group

Description:

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

Treatment:

Drug: Sitagliptin 100mg

Drug: Entresto