Tirzepatide
Approved as Mounjaro (type 2 diabetes, May 2022) and Zepbound (chronic weight management, November 2023).
Tirzepatide simultaneously activates GIP and GLP-1 receptors on pancreatic beta cells and in the brain, enhancing glucose-dependent insulin secretion, suppressing glucagon, slowing gastric emptying, a...
Sequence
Mechanism of Action
Tirzepatide simultaneously activates GIP and GLP-1 receptors on pancreatic beta cells and in the brain, enhancing glucose-dependent insulin secretion, suppressing glucagon, slowing gastric emptying, and reducing food intake. Structural studies show it activates GIPR similarly to native GIP but engages GLP-1R differently, producing less receptor desensitization than native GLP-1. It carries the same boxed warning for thyroid C-cell tumors as other drugs in its class. In the pivotal SURMOUNT-1 trial, mean weight reductions reached 22.5% at the highest dose versus 2.4% for placebo at 72 weeks; gastrointestinal adverse events, especially nausea, were significantly more common than with comparators across a 6-trial meta-analysis.