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Abstract: PO1022

Effects of Semaglutide on CKD Outcomes: A Post Hoc Pooled Analysis from the SUSTAIN 6 and PIONEER 6 Trials

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Tuttle, Katherine R., Institute of Translational Health Sciences, Kidney Research Institute, and Nephrology Division, University of Washington, Seattle, Washington, United States
  • Cherney, David, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Hadjadj, Samy, L'institut du thorax, INSERM, CNRS, University of Nantes, CHU Nantes, Nantes, France
  • Idorn, Thomas, Novo Nordisk A/S, Søborg, Denmark
  • Mosenzon, Ofri, Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel
  • Perkovic, Vlado, University of New South Wales, Sydney, New South Wales, Australia
  • Rasmussen, Soren, Novo Nordisk A/S, Søborg, Denmark
  • Wolthers, Benjamin, Novo Nordisk A/S, Søborg, Denmark
  • Bain, Stephen C., Diabetes Research Unit, Swansea University Medical School, Swansea, United Kingdom
Background

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.

Methods

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.

Results

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.

Conclusion

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.

Funding

  • Commercial Support –