PROJECT SUMMARY/ABSTRACT Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD), accounting for ~47% and ~39% of US incident and prevalent end‐stage kidney disease (ESKD) patients, respectively. Our published research has shown that hypoglycemia is a highly prevalent complication associated with higher death risk in diabetic kidney disease (DKD) patients. Diabetic hemodialysis (HD) patients are at heightened risk for hypoglycemia via multiple pathways, including 1) decreased renal gluconeogenesis, 2) impaired metabolism/ clearance of DM medications, 3) co-existing comorbidities, 4) limited in-center HD food access, and 5) intra- dialytic glucose shifts. Given the ill effects of hypoglycemia on the cardiovascular (CV) health (arrhythmia, myocardial ischemia) and psychological well-being (hypoglycemia fear, stress/anxiety) observed in non-CKD studies, and the poor survival of diabetic HD patients (<35% over 5 years) largely due to CV causes, there is an urgent unmet need to identify strategies that mitigate low glycemic complications in this population. One of the major barriers to optimal glycemic control in DKD has been the lack of access to a practical, reliable method for frequent glycemic assessment. In diabetic HD patients, conventional metrics (self- monitored blood glucose [SMBG], HbA1c) are dominantly used despite limitations in accuracy, convenience, and intermittent frequency. In contrast, continuous glucose monitoring (CGM) is a convenient, automated glycemic assessment method that has shown improved glycemic control and reduced hypoglycemia in non- CKD trials. While our pilot data of CGM in HD patients shows strong agreement with gold-standard blood glucose levels and superior identification of hypoglycemia, it remains uncertain as to whether CGM can improve glycemic control, reduce hypoglycemia, optimize patient-reported outcomes in this population. To address this knowledge gap, we propose this Multiple-PI R01 study in which we aim to conduct a parallel, two-arm randomized controlled trial (RCT) comparing real-time CGM using Dexcom G6 devices vs. usual care (SMBG 4-times/day) among 122 in-center HD patients with DM over a 12-week period. Our primary objective will be to determine the effects of CGM vs. usual care on glycemic control, defined by percent (%) of time in target glucose range (70-180 mg/dl). Our main and exploratory secondary objectives will be to determine the effects of CGM on CGM-indices of hypoglycemia, blood-based glycemic markers (HbA1c, glycated albumin, fructosamine), and patient-reported outcomes (health-related quality of life, diabetes distress, hypoglycemia fear). We will also evaluate feasibility endpoints by measuring CGM compliance during the intervention period and success/ease of implementing CGM training sessions among patients. This single- center pilot RCT is the critical first step in determining the feasibility, efficacy, and safety of CGM in diabetic HD patients, and it will ...