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This limited bioavailability is primarily attributed to AS-IVs relatively large molecular weight, low lipophilicity, and poor intestinal permeability, resulting in suboptimal efficacy for single oral administrations (Jun-Xian et al., 2011)

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TRIUMPH-4 data suggests retatrutide delivers on both fronts, though a dedicated cardiovascular outcomes trial running through 2027-2028 will provide definitive proof