Effect of Neprilysin on Glucagon-Like Peptide-1 in Patients With Type 2 Diabetes (NEPT2D)

University of Copenhagen

Status and phase: Completed; Phase 4

Conditions: Type2 Diabetes

Treatments: Drug: Placebo; Drug: Sitagliptin; Drug: Valsartan; Drug: Entresto

Study type: Interventional

Funder types: Other

Identifiers

NCT03893526

NEPT2D

Details and patient eligibility

About

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

Enrollment: 12 patients

Sex: Male

Ages: 30 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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12 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants are subjected to a standardized meal

Treatment:

Drug: Placebo

Entrestro

Active Comparator group

Description:

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

Treatment:

Drug: Entresto

Sitagliptin

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

Entrestro + sitagliptin

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: Entresto

Drug: Sitagliptin

Valsartan

Active Comparator group

Description:

206mg valsartan as one single dose followed by a standardized meal

Treatment:

Drug: Valsartan