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How Tirzepatide Compares Mechanistically to Semaglutide and Liraglutide | Feature | Tirzepatide | Semaglutide | Liraglutide | |---|---|---|---| | Receptor targets | GIP-R + GLP-1R | GLP-1R only | GLP-1R only | | Half-life | ~5 days | ~7 days | ~13 hours | | Dosing frequency | Weekly | Weekly | Daily | | Max approved weight loss dose | 15 mg | 2.4 mg (Wegovy) | 3 mg (Saxenda) | | Mean weight loss (key trial) | 20.9% (SURMOUNT-1) | 14.9% (STEP-1) | 5.8% (SCALE) | | Biased GLP-1R agonism | Yes (low beta-arrestin) | Partial | Lower | | Adipose GIPR mechanism | Yes | No | No | The 6-percentage-point gap in mean weight loss between tirzepatide and semaglutide in their respective Phase III key trials reflects the additive adipose and hypothalamic contributions of GIPR engagement [34]