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Taken together, the figure highlights a key mechanistic principle underlying the therapeutic rationale for multi-agonist strategies: while GLP-1R monotherapy achieves meaningful metabolic and hepatic benefits exclusively through indirect, systemic pathways, the addition of GIPR and - most importantly - GCGR co-agonism introduces complementary and increasingly direct hepatic mechanisms, providing the pharmacological basis for the superior efficacy observed with dual and triple agonists in MASLD/MASH
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doi: 10.1016/j.jep.2024.118517 204 ZhouYHuTZengHLinLXieHLinRet al
The documented reasons, in order: side effects - most pronounced during titration and most manageable with responsive clinical support - followed by cost, followed by a mix of access, supply, and personal circumstance
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They found that low dose EX-4 treatment may protect the -cells from apoptosis, consequently increased the number of the -cells
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