Effects of Semaglutide on CKD Outcomes: A Post Hoc Pooled Analysis from the SUSTAIN 6 and PIONEER 6 Trials
ASN Kidney Week
The SUSTAIN 6 cardiovascular outcomes trial (CVOT) indicated a benefit on kidney disease with subcutaneous (s.c.) once-weekly (OW) semaglutide vs placebo (PBO) in subjects with type 2 diabetes (T2D) at high CV risk. The PIONEER 6 CVOT reported CV safety with oral once-daily (OD) semaglutide in a similar cohort. This post hoc analysis evaluated the potential benefit of semaglutide vs PBO on chronic kidney disease (CKD) outcomes.
Data from 6,480 subjects (SUSTAIN 6: N=3,297; median follow-up, 2.1 years; mean baseline [BL] estimated glomerular filtration rate [eGFR], 76 mL/min/1.73 m2; PIONEER 6: N=3,183; median follow-up, 1.3 years; mean BL eGFR, 74 mL/min/1.73 m2) were pooled for semaglutide (0.5 and 1.0 mg s.c. OW, 14 mg oral OD) or PBO. Time to onset of persistent eGFR reduction (≥30, ≥40, ≥50, ≥57% [corresponding to doubling of serum creatinine]) was evaluated overall and by BL eGFR subgroup (≥30–<60, ≥60 mL/min/1.73 m2). Analyses used a Cox proportional-hazards model with treatment group and eGFR subgroup and interaction between both as fixed factors stratified by trial.
In the overall population, hazard ratios (HRs) for onset of persistent eGFR reductions with semaglutide vs PBO were not statistically significantly different from 1, but estimated HRs were <1.0, favoring semaglutide. Estimated HRs for semaglutide vs PBO in the eGFR ≥30–<60 mL/min/1.73 m2 subgroup were generally lower than in the overall population; semaglutide significantly reduced the risk of developing a persistent 30% eGFR reduction vs PBO (p=0.03; Figure). No significant interactions between treatment and eGFR subgroup were observed.
This analysis of semaglutide CVOTs supports the possibility of a smaller magnitude of eGFR decline with semaglutide vs PBO and suggests a potential kidney disease benefit of semaglutide vs PBO in people with T2D and established CKD.
Kidney & Diabetes
Tuttle, Katherine; Cherney, David; Hadjadj, Samy; Idorn, Thomas; Mosenzon, Ofri; Perkovic, Vlado; Rassmussen, Soren; Wolthers, Benjamin; and Bain, Stephen C., "Effects of Semaglutide on CKD Outcomes: A Post Hoc Pooled Analysis from the SUSTAIN 6 and PIONEER 6 Trials" (2020). Articles, Abstracts, and Reports. 3956.