Metformin Use and Clinical Outcomes in Autosomal Dominant Polycystic Kidney Disease: A Nationwide Cohort Study

<b>Background/Objectives</b>: Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic disorder marked by bilateral renal cysts and extrarenal manifestations, ultimately resulting in renal failure. Emerging research indicates that metformin might influence the intracellular mechanisms of ADPKD, though its clinical significance remains uncertain. <b>Methods</b>: We applied the Taiwan National Health Insurance Database (NHIRD) to investigate the clinical impact of metformin utilization in ADPKD patients in real-world practice. The metformin user group was defined by more than 90 days of usage. To mitigate selection bias, we established a non-user group with a 1:2 ratio, matching for age, sex, and comorbidities by a propensity score matching method. <b>Results</b>: A total of 10,222 ADPKD cases were identified in the NHIRD between 2009 and 2018. After matching, the metformin user group was composed of 778 cases with a mean age of 59.5 ± 13.9 years, and the non-user group of 1546 cases with a mean age of 59.3 ± 14.4 years. The time from the index date to the outcome of ESKD in ADPKD was 5.3 ± 2.2 years in the metformin user group and 5.3 ± 2.3 years in the metformin non-user group, respectively. The metformin user group exhibited a significant reduction in the risk of end-stage kidney disease (ESKD), as indicated in the fully adjusted model (0.75, 95% CI 0.58-0.97, <i>p</i> = 0.03). A decreased risk of major adverse cardiovascular events (MACEs) was noted in metformin users, with an adjusted hazard ratio (HR) of 0.78 (95% CI 0.65-0.95, <i>p</i> = 0.01). Sensitivity analysis showed similar results by excluding late-stage CKD (CKD stage 5 or erythropoietin-stimulating agents use). <b>Conclusions</b>: Metformin usage in real-world practice showed lower hazards of ESKD and MACEs in patients with ADPKD, except for those with advanced CKD.