PYY1-36 + sitagliptin

PYY1-36 + sitagliptin is an experimental combination therapy consisting of peptide YY 1-36 (PYY1-36), a naturally occurring gut hormone, and sitagliptin, a small molecule dipeptidyl peptidase 4 (DPP4) inhibitor. PYY1-36 acts primarily as an agonist at the neuropeptide Y receptor Y1 (Y1R), influencing appetite regulation, glucose metabolism, and cardiac fibroblast activity. Sitagliptin inhibits DPP4, the enzyme responsible for degrading PYY1-36 to its inactive form (PYY3-36), thereby prolonging the biological activity of PYY1-36. The combination has been studied in preclinical and early clinical settings for its effects on metabolic parameters such as glucose homeostasis and insulin secretion, as well as on cardiac fibroblast proliferation and collagen production[2][4][6]. This approach aims to enhance the beneficial actions of endogenous or exogenous PYY1-36 by preventing its rapid enzymatic breakdown.