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doi:10.1016/j.ajo.2025.02.025 34
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
Oral semaglutide may feel gentler initially because it avoids the rapid injection bolus, but it still causes nausea in roughly 2025% of patients due to the same gastric-slowing mechanism
Neurological Symptoms Several Weeks to Months If you have tingling, numbness in your hands or feet, or balance problems caused by B12 deficiency, these symptoms take longer to improve
Pathophysiologically, MASLD is strongly associated with insulin resistance, leading to hepatic lipid accumulation, inflammation, and in advanced stages, fibrosis and cirrhosis
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