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Abstract: PO1020

Once-Weekly Exenatide Effects on eGFR Slope and Urine Albumin-to-Creatinine Ratio (UACR) as a Function of Baseline UACR: An EXSCEL Post Hoc Analysis

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Clegg, Lindsay, Clinical Pharmacology & Quantitative Pharmacology, R&D, AstraZeneca, Gaithersburg, Maryland, United States
  • Aart, van der, Annemarie B., Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, Netherlands
  • Penland, Robert C., Clinical Pharmacology & Quantitative Pharmacology, R&D, AstraZeneca, Boston, Massachusetts, United States
  • Boulton, David W., Clinical Pharmacology & Quantitative Pharmacology, R&D, AstraZeneca, Gaithersburg, Maryland, United States
  • Sjostrom, David, Late-stage Development CVRM, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
  • Mentz, Robert J., Duke University and Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States
  • Rury, Holman, Diabetes Trials Unit, University of Oxford, Oxford, United Kingdom
  • L Heerspink, Hiddo Jan, Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, Netherlands
Background

GLP-1 RA effects on major kidney outcomes in unselected T2D patients at high cardiovascular (CV) risk are modest or neutral. However, GLP-1 RA may provide renal benefits in those at high risk of worsening kidney disease. We examined once-weekly exenatide (EQW) effects on eGFR slope and UACR change, as a function of baseline UACR, in a subset of EXSCEL participants.

Methods

Of 14752 EXSCEL participants, eGFR slope was assessed in those with baseline UACR and ≥1 post-baseline eGFR (n=3503 [23.7%]) via mixed model repeated measures (MMRM) analysis (median follow-up 3.3 years). UACR percent change from baseline to first post-baseline measurement (median time 8.9 months) was assessed in those with baseline and ≥1 follow-up UACR (n=2828 [19.2%]) via ANCOVA of log-transformed UACR, with baseline UACR as a covariate.

Results

Participants with baseline UACR measurements were generally similar to the overall EXSCEL population, and balanced across treatment arms. EQW improved eGFR slope, compared with placebo, in patients with baseline UACR>100mg/g (+0.79 mL/min/1.73m2/year [95% CI 0.24–1.34]) and UACR>200mg/g (+1.32 mL/min/1.73m2/year 95% CI [0.57–2.06], but not at lower UACR thresholds (Figure A). No difference in EQW effect on eGFR was observed as a function of baseline eGFR, CV disease history, RAAS inhibitor use, or SBP. EQW, compared with placebo, reduced UACR by 28.2% in patients with baseline UACR>30 mg/g. This effect was consistent in subgroups with higher baseline UACR (baseline UACR>100 mg 22.5%; baseline UACR>200 mg 34.5%) (Figure B).

Conclusion

This post-hoc EXSCEL analysis suggests that EQW reduces UACR, with improvement in eGFR slope specifically in participants with elevated baseline UACR.

Funding

  • Commercial Support