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JCI Insight 9 , e172152 (2024)

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Researchers should also recognize that the combinations per-unit efficiency means that a well-designed combination protocol frequently achieves a larger research signal at a lower total compound cost than a single-compound protocol producing the same effect, which is part of why the combination dosing approach dominates the published GH-axis research literature

This can add up to more oxidative stress on the body

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

Sadiur Rahman Sajon et al