Why Natural GLP-1 Disappears So Fast: DPP-4, Half-Life, and How Ozempic-Style Drugs Are Engineered

GLP-1 is a gut-derived hormone designed to signal the pancreas to produce insulin—but in its natural form, it’s notoriously short-lived. In this Decoding Health segment, we break down why endogenous GLP-1 has an ultra-short half-life (about three minutes), and how the enzyme DPP-4 rapidly “clips” incretin hormones by targeting specific amino acids near the N-terminus—effectively destroying the signal before it can last.

You’ll learn how GLP-1 receptor agonist drugs were engineered to resist DPP-4 degradation, why DPP-4 inhibitor medications (the “gliptins”) extend incretin activity from a different angle, and why measuring GLP-1 in blood samples is scientifically challenging due to ongoing enzyme activity even after blood is drawn. This episode clarifies the biology behind incretins, insulin signaling, and why drug design focuses on stability—while separating the molecule’s function from the controversy around how these therapies are used today.