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At MC4R, the hypothalamic Gs pathway combined with ERK1/2 pathways and modulation of ion channels (ATP-sensitive potassium channel Kir6.2) underpins satietogenic signaling

A landmark 2023 study published in JAMA found that GLP-1 agonist users experienced increased risks of gastrointestinal adverse events (with gastroparesis risk elevated compared to patients using other diabetes medications), while a 2024 case report in PMC documented the strong relationship between semaglutide use and gastroparesis symptoms that resolved only after drug discontinuation

nevertheless, given that the current evidence stems primarily from small, nonrandomized cohort studies, the efficacy, optimal target populations, and long-term safety of this treatment must be further investigated through prospective, controlled studies based on standardized protocols 177

(2005) 289:H24018

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