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...
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.
Medicine (Baltimore) · 2023
Meta-analysis of 6 trials (4,586 patients) found significantly higher gastrointestinal adverse events, notably nausea, versus comparators.
View Source →Proceedings of the National Academy of Sciences · 2022
Cryo-EM and signaling assays explain the differential GIPR/GLP-1R engagement underlying tirzepatide's efficacy.
View Source →New England Journal of Medicine · 2022
SURMOUNT-1 found mean weight reductions of 16.0%/21.4%/22.5% across doses versus 2.4% for placebo at 72 weeks.
View Source →New England Journal of Medicine · 2021
SURPASS-2 found tirzepatide noninferior/superior to semaglutide 1 mg for HbA1c reduction at 40 weeks, with greater weight loss.
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