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The primary drawback is practicality

SGLT-2 inhibitors are antihyperglycemic agents that target SGLT-2 proteins expressed in the proximal convoluted tubules of the kidneys, where they normally mediate the reabsorption of glucose from the urine

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First, there was considerable cytoplasmic -ketoglutarate production coupled with serine synthesis (flux in excess of that required for malic enzyme), minimal matrix -ketoglutarate produced from citrate, and relatively high cytoplasmic malate consumption by malic enzyme, all of which could make the metabolite gradients favorable for reverse transport by the -ketoglutarate carrier