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The findings of the REDEFINE 1 and REDEFINE 2 trials reinforce the pivotal role of combination pharmacotherapy by targeting diverse mechanisms of action that translate into improved weight loss achievements as well as an impact on complications

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Neuroplasticity driven by HGF/c-Met signaling includes upregulation of brain-derived neurotrophic factor (BDNF), activation of postsynaptic density protein-95 (PSD-95), and increased expression of GluN2B-containing NMDA receptors

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Proposed pathways include modulation of multiple neurotransmitter systems (influencing serotonin, dopamine, norepinephrine, GABA, glutamate levels), possible involvement of NMDA receptors, alpha-1 adrenergic signaling (e.g., potentiating pineal acetyltransferase activity), inhibition of somatostatin release via dopaminergic routes, reduced ACTH/cortisol for stress buffering, and stimulated growth hormone or somatoliberin secretion