Role of Normal Protein Catabolic Rate (nPCR) in Predicting Weight Loss among Patients on Hemodialysis Treated with Tirzepatide

Background: Tirzepatide, a novel dual GLP-1/GIP receptor combination, shows promising potential for treating type 2 diabetes mellitus (T2DM) by inducing weight loss, albeit with variable efficacy among individuals. In HD patients, establishing appropriate dry weight (DW) parameters is crucial, as spontaneous weight fluctuations are uncommon. This study aims to identify optimal parameters for setting DW in patients undergoing HD on tirzepatide treatment. Methods: Twenty-three stable type 2 diabetic patients undergoing outpatient maintenance HD, already on existing GLP-1 receptor agonists, were enrolled. Mean age was 63.8 years, with 18 males and 5 females, and mean dialysis history of 5.6 years. Patients transitioned from existing GLP-1 receptor agonists to tirzepatide, with the correlation between the rate of DW reduction, clinical symptoms, and changes in various nutritional indices assessed over a 6-month period. Results: Mean DW decreased significantly from 72.7kg to 70.3kg over 6 months, with an average weight loss of -2.6kg (-3.9%). Notably, a considerable variation in weight change was observed (standard deviation: 2.28; coefficient of variation: -0.851). Among nutritional indices, only nPCR demonstrated a significant correlation with weight loss (r=-0.44, p=0.04), indicating greater weight loss in patients with decreased nPCR (Figure). Conclusion: While serum phosphorus and potassium levels are commonly used to estimate appetite and food intake in hemodialysis patients, they did not exhibit significant correlation with changes in body weight. Conversely, nPCR, reflecting dietary protein intake, showed the strongest correlation with weight changes during tirzepatide administration. Monitoring nPCR can enable early detection of appetite loss and facilitate adjustments in DW, potentially mitigating complications like pulmonary congestion and pleural effusion associated with tirzepatide use in HD patients. Funding: NIDDK Support, Private Foundation Support