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Key findings: CagriSema achieved up to 23% weight loss at 84 weeks Tirzepatide showed numerical superiority (~25.5%) The trial did not meet non-inferiority vs tirzepatide Clinical interpretation: Despite not meeting the primary endpoint, an important signal emerges: targeting multiple biological pathways remains a compelling strategy Why this matters: Reinforces obesity as a complex neuroendocrine disease Supports the concept that multi-hormonal approaches may better impact the defended weight set point Moves the field closer to precision, mechanism-based therapies Safety: Consistent with the GLP-1 class Mainly gastrointestinal adverse events, generally mild to moderate and transient Whats next: Ongoing development with higher-dose CagriSema Expansion of the REDEFINE program FDA decision expected by late 2026 Take-home message: The future of obesity treatment lies not in a single pathway, but in strategically combining mechanisms to sustainably shift weight biology

doi: 10.1007/s13238-020-00804-9 93 KangS.ParkM

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