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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
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | No treatment. Participants are subjected to a standardized meal |
|
| Entrestro as single dose | Active Comparator | 194 mg sacubitril / 206 mg valstartan (entresto) as one single dose followed by a standardized meal |
|
| Sitagliptin as single dose | Active Comparator | 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 | Active Comparator | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Entresto | Drug | Single dose administration of Entrestro 194 mg sacubitril / 206 mg valstartan |
|
| 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) |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Blood glucose | changes in blood glucose using immunological methods | 3 hours after treatment and during the subsequent standardized meal |
| GIP | changes in plasma GIP using immunological methods |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Copenhagen | Copenhagen | 2100 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31074791 | Result | Wewer Albrechtsen NJ, Mark PD, Terzic D, Hansen LH, Andersen UO, Hartmann B, Carr RD, Gustafsson F, Deacon CF, Holst JJ, Goetze JP, Plomgaard P. Sacubitril/Valsartan Augments Postprandial Plasma Concentrations of Active GLP-1 When Combined With Sitagliptin in Men. J Clin Endocrinol Metab. 2019 Sep 1;104(9):3868-3876. doi: 10.1210/jc.2019-00515. | |
| 35175317 |
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undecided
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C549068 | sacubitril and valsartan sodium hydrate drug combination |
| D000068900 | Sitagliptin Phosphate |
| D054873 | Dipeptidyl-Peptidase IV Inhibitors |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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The participants are on 4 study days with wash out period of minimum 2 weeks randomized to 4 intervention arms
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|
| Sitagliptin 100mg | Drug | 2 x 100mg sitagliptin as single dose. |
|
|
| Placebos | Drug | No treatment |
|
|
| 3 hours after treatment ( during the subsequent standardized meal) |
| 3 hours after treatment ( during the subsequent standardized meal) |
| Thonsgaard S, Prickett TCR, Hansen LH, Wewer Albrechtsen NJ, Andersen UO, Terzic D, Plomgaard P, Gustafsson F, Goetze JP, Mark PD. Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men. Clin Chem. 2022 May 18;68(5):713-720. doi: 10.1093/clinchem/hvac005. |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D011719 |
| Pyrazines |
| D011480 | Protease Inhibitors |
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D007004 | Hypoglycemic Agents |
| D045505 | Physiological Effects of Drugs |