BRENZAVVY Safety and Effectiveness in Patients with Stage 3 Chronic Kidney Disease (CKD)
Study Design
A phase 3, randomized, double-blind, placebo-controlled trial evaluated the effectiveness and safety of BRENZAVVY, 20 mg, in adults with type 2 diabetes mellitus, moderate renal impairment (stage 3 CKD) and inadequate glycemic control. 312 adults received BRENZAVVY, 20 mg, or placebo in addition to ongoing hypoglycemic medications for 24 weeks. Eligible patients were stratified based on their estimated glomerular filtration rate (eGFR; either 30 to < 45 mL min-1 per 1.73 m2, stage 3b CKD, or 45 to < 60 mL min-1 per 1.73 m2, stage 3a CKD), baseline HbA1c (> 8.5% or not) or use of insulin. The primary endpoint was the change in HbA1c from baseline to week 24.
Study Population
At baseline, 166 patients had CKD stage 3a while 146 had CKD stage 3b. The average age was 69.6 years. Enrolled patients had an average duration of diabetes of approximately 16 years, a mean baseline HbA1c level of 7.98%, and a mean BMI of 30.2 kg m-2. Approximately 56% of patients were prescribed insulin prior to study participation and were instructed to continue their insulin dosing throughout their participation in the study. 37% of patients had normal albuminuria (UACR < 30 mg g-1), 38% had moderately increased albuminuria (UACR 30-299 mg g-1) and 25% had severely increased albuminuria (UACR ≥ 300 mg g-1).
HbA1c
BRENZAVVY treatment improved glycemic control in patients with moderate renal impairment. The reduction of 0.61% from baseline HbA1c and the placebo-corrected treatment effect of −0.37% was clinically meaningful and statistically significant. Rescue medication was provided to 26 patients (9 in the BRENZAVVY arm and 17 in the placebo arm). Including observed values after treatment with rescue medication showed a reduction of 0.59% from baseline HbA1c and a placebo-corrected treatment effect of −0.28%.
Body Mass
247 adults in the randomized population had a baseline BMI ≥ 25 kg m-2. Following 24 weeks of treatment with BRENZAVVY or placebo, a reduction in the mean body weight was observed in both arms. The placebo-adjusted change in the BRENZAVVY arm was −1.76 kg and was statistically significant.
Urine Albumin to Creatinine Ratio (UACR)
Decreased albuminuria was observed in patients treated with BRENZAVVY. A statistically significant placebo-adjusted geometric mean ratio reduction in the UACR of 20.1% was observed in the BRENZAVVY arm.
REFERENCES: 1. Allegretti AS, Zhang W, Zhou W, et al. Safety and Effectiveness of Bexagliflozin in Patients With Type 2 Diabetes Mellitus and Stage 3a/3b CKD. Am J Kidney Dis. 2019;74(3):328-337. doi:10.1053/j.ajkd.2019.03.417; PMID: 31101403; PMCID: PMC10077840.