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Tolrestat and epalrestat have been characterized as noncompetitive inhibitors of aldo‐ketone reductase 1B1 (AKR1B1), a leading drug target for the treatment of type 2 diabetes complications. However, clinical applications are limited for most AKR1B1 inhibitors due to adverse effects of cross‐inhibition with other AKRs. Here, we report an atypical competitive binding and inhibitory effect of tolrestat...