SGLT2 inhibition for patients with ADPKD – closing the evidence gap

Abstract Inhibitors of the sodium-glucose cotransporter 2 (SGLT2i) were originally developed to treat diabetes mellitus but have shown important renoprotective benefits independently from blood glucose levels. SGLT2i have thus become an important addition to the therapeutic armamentarium to treat patients with chronic kidney disease. However, specific patient populations were excluded from the pivotal trials, for instance patients with very low eGFR, patients on dialysis, kidney transplant recipients and patients with autosomal dominant polycystic kidney disease (ADPKD), the most common genetic kidney disorder. Considering the lack of potent treatment modalities in ADPKD, the use of SGLT2i in this patient population would be of major interest. However, the combination of inconclusive results from preclinical models with the lack of clinical efficacy data and potential disease-specific safety concerns currently exclude patients with ADPKD from this promising therapeutic opportunity. This results in an urgent need for adequately powered clinical trials examining SGLT2i in ADPKD. This review summarizes the current knowledge on SGLT2i in this specific patient population and outlines running and upcoming clinical trial programs in different geographic regions aiming to make SGLT2i accessible to patients with ADPKD.