Diagram of the mechanism of action of PKD treatment in miniature pigs with the combination of 2DG and metformin. In the renal tissues of miniature pigs with polycystic kidneys, the level of glycolysis is significantly increased, leading to a higher production of ATP and decreased expression of p‐AMPK. These effects in turn induce the elevated expression of p‐ERK, p‐mTOR, p‐p70S6K and p‐4EBP1 and significantly enhance cell proliferation. The combination of 2DG and metformin for the treatment of miniature pigs with PKD blocks glycolysis, suppresses ATP production and increases p‐AMPK activity. In addition, this treatment strategy reduces the activities of p‐ERK, p‐mTOR, p‐p70S6K and p‐4EBP1, significantly inhibiting the proliferation of tubular cystic epithelial cells. p‐ (phospho‐) indicates the activated state of the protein.