Tirzepatide

Modified GIP/GLP-1 dual agonist · C₂₂₅H₃₄₈N₄₈O₆₈

Mechanism of Action

Tirzepatide is a single molecule that acts simultaneously on both the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), a mechanism termed “twincretin” activity. This dual engagement produces synergistic metabolic effects exceeding those of selective GLP-1 agonism alone.

GIP Receptor Activation

The GIP receptor is expressed in the pancreas, adipose tissue, bone, and brain. GIP receptor stimulation augments glucose-dependent insulin secretion and directly promotes adipocyte lipolysis — the latter potentially explaining tirzepatide’s superior fat mass reduction compared to pure GLP-1 agonists.

GLP-1 Receptor Activation

Through GLP-1R engagement, tirzepatide slows gastric emptying, reduces glucagon secretion, and activates central hypothalamic circuits governing satiety — resulting in profound reduction in caloric intake.

SURMOUNT-1 Data

In the SURMOUNT-1 Phase III trial, once-weekly 15 mg tirzepatide produced mean weight loss of 22.5% over 72 weeks in non-diabetic obese adults — the highest efficacy reported for any approved anti-obesity pharmacotherapy at the time of publication.