SGLT2 Inhibitors in Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Meta-Analysis

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, with tolvaptan remaining the primary disease-modifying therapy. SGLT2 inhibitors have demonstrated robust renoprotection across the chronic kidney disease (CKD) spectrum, yet patients with ADPKD have been systematically excluded from pivotal trials due to concerns over vasopressin-mediated cystogenesis. This systematic review and meta-analysis aimed to pool available evidence on SGLT2 inhibitor use in patients with ADPKD. This systematic review and meta-analysis were registered with PROSPERO (CRD420261324155) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta‑Analyses (PRISMA) guidelines. Five databases were searched through February 2026 for studies including ADPKD patients receiving any SGLT2 inhibitor. Quality was assessed using the Risk of Bias 2 (RoB2), Newcastle-Ottawa Scale, and Joanna Briggs Institute (JBI) tools, depending on the study design. Eight studies encompassing 3,180 patients were included, comprising one randomized controlled trial (RCT), one target trial emulation study, and six retrospective observational studies. In comparative analyses, SGLT2 inhibitor use was associated with a statistically significant attenuation of estimated glomerular filtration rate (eGFR) decline (pooled mean difference {MD}: 1.344 mL/min/1.73 m²/year; 95% CI: 0.836-1.852). A significant hemoglobin increase was observed in both comparative (MD: 0.66 g/dL) and single-arm analyses (MD: 0.55 g/dL). Subgroup analyses suggested a greater eGFR benefit in non-diabetic patients, though differences were not statistically significant. Our findings suggest that SGLT2 inhibitors may attenuate eGFR decline and improve hemoglobin in ADPKD, with the initial eGFR dip representing a class effect rather than harm, supporting their prospective evaluation in dedicated randomized trials. These findings should be interpretedwith cuchion the predominantly observational study designs, heterogeneous patient populations.