1808-P: RAAS Inhibitor-Stratified Efficacy of Sodium Zirconium Cyclosilicate vs. Potassium-Restricted Diet and Nutritional Trade-Offs in Type 2 Diabetes: A SILVERSTAR Subanalysis

Introduction and Objective: Hyperkalemia limits guideline-directed RAAS inhibitor (RAASi) therapy. Potassium restriction may reduce diet quality, including fiber intake. In the SILVERSTAR trial, sodium zirconium cyclosilicate (SZC) did not meet noninferiority to diet in the prespecified full analysis set, although supportive analyses favored SZC. This subanalysis examined whether baseline RAASi use modifies the effectiveness of SZC vs a potassium-restricted diet for maintenance-phase normokalemia and assessed diet-related fiber changes. Methods: Multicenter, open-label RCT (jRCTs051230067). After a common SZC loading phase, adults with type 2 diabetes (T2D) and hyperkalemia were randomized to SZC maintenance therapy or a potassium-restricted diet. The primary endpoint was normokalemia (3.5-<5.0 mEq/L) at Visit 7 (V7). This post hoc analysis stratified outcomes by baseline RAASi use. Diet quality was assessed using the BDHQ at V1 and V7. P values are nominal. Results: Among RAASi users, normokalemia occurred in 84.0% with SZC (21/25) vs 56.5% with diet (13/23) (χ² P=0.036; Fisher P=0.060). Among non-users, rates were 63.6% (7/11) vs 86.7% (13/15) (Fisher P=0.35). Diet-based restriction reduced total, soluble, and insolable fiber, whereas SZC preserved fiber intake. Between-group differences favored SZC across all fiber components. As RAASi therapy remained stable, fiber reductions reflect diet restriction rather than RAASi status. Conclusion: In T2D with hyperkalemia, SZC showed greater benefit among RAASi users for achieving maintenance-phase normokalemia. Potassium-restricted diets consistently reduced dietary fiber, representing a clinically relevant nutritional trade-off independent of RAASi use. These findings support a stepwise strategy that treats hyperkalemia to preserve both RAASi therapy and overall diet quality. Disclosure M. Yoneda: None. H. Okada: None. Y. Hashimoto: None. M. Hamaguchi: Research Support; Current; AstraZeneca, Kowa Company, Ltd. M. Fukui: None. A. Kobayashi: None. A. Kitae: None. M. Asano: None. J. Hironaka: None. A. Kishi: None. N. Kitagawa: None. M. Ishii: None. M. Yamazaki: None. T. Tanaka: None. H. Nakajima: None. E. Sato: None.