Effects of veverimer on serum bicarbonate and physical function in diabetic patients with chronic kidney disease and metabolic acidosis: subgroup analysis from a randomized, controlled trial.

BACKGROUND Metabolic acidosis is a complication of chronic kidney disease (CKD) that increases risk of CKD progression, causes bone demineralization and muscle protein catabolism. Patients with diabetes are prone to metabolic acidosis and functional limitations that decrease quality of life. Veverimer, an investigational, non-absorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as treatment for metabolic acidosis. This post hoc subgroup analysis evaluated effects of veverimer on metabolic acidosis and physical function among patients with diabetes. METHODS This was a Phase 3, multicenter, randomized, blinded, placebo-controlled trial in 196 patients with CKD (eGFR: 20-40 mL/min/1.73 m2) and metabolic acidosis who were treated for up to 1 year with veverimer or placebo. RESULTS At week 52, veverimer-treated patients with diabetes (n = 70), had a significantly greater increase in mean serum bicarbonate than the placebo group (n = 57) (4.4 vs. 2.9 mmol/L; P < 0.05). Patient-reported limitations of physical function on the Kidney Disease and Quality of Life - Physical Function Domain (e.g., walking several blocks, climbing a flight of stairs) improved significantly in the veverimer vs. placebo group (+12.5 vs. +0.3, respectively, P < 0.001) as did objective physical performance on the repeated chair stand test (P < 0.0001). CONCLUSIONS Few interventions for patients with diabetes and CKD have successfully improved quality of life or physical functioning. Our study demonstrated that veverimer effectively treated metabolic acidosis in patients with diabetes and CKD, and significantly improved how these patients felt and functioned.