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The PIONEER 2 and 3 trials enrolled patients with diabetes with HbA1c values between 7.0% and 10.5%, and PIONEER 4 enrolled patients with diabetes with HbA1c values between 7.0% and 9.5%

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Mechanistically, -KG decreases Treg differentiation by inhibiting FOXP3 and upregulating inflammatory cytokines such as IFN-, Tbet, and Rorc, suggesting that Th1-type effector T cells are more dependent on glutaminolysis than Treg cells 136

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This is followed by additional scientific findings that when precipitated by solvent exchange or when supernatant solutions are left in contact with the excess solid material, niclosamide readily reverts to more stable and lower solubility polymorphs

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