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

Summary

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

Timeline

Start

2019-01-25

Primary completion

2021-03-01

Completion

2021-03-01

Publications

• Wewer Albrechtsen NJ, Moller A, Martinussen C, Gluud LL, Rashu EB, Richter MM, Plomgaard P, Goetze JP, Kjeldsen S, Hansen LH, Gustafsson F, Deacon CF, Holst JJ, Madsbad S, Bojsen-Moller KN. Acute effects on glucose tolerance by neprilysin inhibition in patients with type 2 diabetes. Diabetes Obes Metab. 2022 Oct;24(10):2017-2026. doi: 10.1111/dom.14789. Epub 2022 Jul 21.

Drugs

Indications