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Long-term outcomes (cardiovascular events, incident diabetes, all-cause mortality) are accessible only through observational cohort studies with follow-up periods of 10–30 years (97, 98), and the inability to reconcile short-term RCT mechanistic data with long-term observational associations represents a fundamental epistemic gap in this field

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Data availability The data that support the findings of this study are openly available in Protein Data Bank (PDB) at PDB ID: 8PDD, 8PL0, 8PL1, 8PL2, 8PL3, 8PL4, 8PL5, 8PL6, 8PL7, 8PL8, 8PL9, 8PLA, 8PLB, 8PLC, 8PLD, 8PLE, 8PLF, 8PLG, 8PLH, 8PLI, 8PLJ, 8PLK, 8PLL, 8PLM, 8PLN, 8PLO, 8PLP, 8PLQ, 8PLR, 8PLS, 8PLT, 8PLU, 8PLV, 8PLW, 8PLX, 8PLY