Tirzepatide is a synthetic peptide with glucose-lowering effects. It
works to stimulate first- and second-phase insulin secretion, and reduces
glucagon levels, both in a glucose-dependent manner. Tirzepatide was also shown to delay gastric
emptying, lower fasting and postprandial glucose concentration, decrease food
intake and reduce body weight in patients with type 2 diabetes. Tirzepatide can
increase insulin sensitivity. As the peptide is conjugated to a C20 fatty diacid
moiety through a hydrophilic linker at the lysine residue at position 20, the
drug is highly bound to albumin in the plasma, which prolongs its half-life. Glucagon-like peptide-1 (GLP-1) receptors (GLP-1R)
are expressed throughout the body, including pancreatic beta-cells and the
gastrointestinal tract. They have been implicated in the pathophysiology of
type II diabetes mellitus as GLP-1R signalling is involved in glucose control
by enhancing glucose-stimulated insulin secretion, delaying gastric transit,
decreasing plasma glucagon levels, and reducing body weight by activating
anorexigenic pathways in the brain. Both glucose-dependent insulinotropic
polypeptide (GIP) and GLP-1 are peptide hormones involved in glucose
homeostasis: they promote glucose-stimulated insulin secretion from the
pancreatic beta-cells. However, GIP is the main incretin hormone that exerts
insulinotropic effects in response to food intake.
