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The anti-inflammatory pathways modulated by GLP-1 receptor activation (NF-kB suppression, macrophage polarization, Treg enhancement) are largely distinct from the pathways targeted by: Methotrexate: Folate metabolism disruption, different anti-inflammatory pathway TNF inhibitors (adalimumab, etanercept): Direct TNF blockade, whereas GLP-1 reduces TNF production upstream IL-6 inhibitors (tocilizumab): Receptor-level blockade, while GLP-1 reduces IL-6 production JAK inhibitors (tofacitinib, baricitinib): Different signaling pathway entirely Corticosteroids: Broad immunosuppression, while GLP-1 is immunomodulatory This pathway complementarity is why additive benefit is biologically plausible

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First, we investigated whether NTAPP has a cytotoxic effect by using the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay at different plasma doses in various exposure time (45, 90, 135, 270 s)