Kidney Week

Abstract: FR-PO317

Effect of Sotagliflozin on eGFR Slope by Baseline Kidney Function and Glycemic Control

Session Information

• Diabetic Kidney Disease: Clinical Modeling, Diagnosis, Education, and More
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Sridhar, Vikas, University of Toronto, Toronto, Ontario, Canada

Vikas Sridhar, MD

• Bhatt, Deepak L., Icahn School of Medicine at Mount Sinai, New York, New York, United States

Deepak L. Bhatt, MD, MPH

• Odutayo, Ayodele, University of Toronto, Toronto, Ontario, Canada

Ayodele Odutayo, MD, MS, MSc, PhD

• Szarek, Michael, SUNY Downstate Health Sciences University, New York City, New York, United States

Michael Szarek, PhD

• Davies, Michael J., Lexicon Pharmaceuticals Inc, The Woodlands, Texas, United States

Michael J. Davies, PhD

• Banks, Phillip, Lexicon Pharmaceuticals Inc, The Woodlands, Texas, United States

Phillip Banks, MS

• Pitt, Bertram, University of Michigan, Ann Arbor, Michigan, United States

Bertram Pitt, MD

• Steg, Philippe Gabriel, Universite Paris Cite, Paris, Île-de-France, France

Philippe Gabriel Steg

• Cherney, David, University of Toronto, Toronto, Ontario, Canada

David Cherney, MD, PhD

Background

In a secondary analysis of the SCORED trial using the complete laboratory dataset, sotagliflozin (SOTA), a dual SGLT1 & 2 inhibitor, reduced the risk of kidney and cardiorenal composite endpoints in patients with type 2 diabetes (T2D) and diabetic kidney disease (DKD). This post hoc analysis of SCORED evaluated the effect of SOTA versus placebo on eGFR slope and the impact of baseline kidney function and glycemia.

Methods

We derived the acute eGFR slope (from baseline to week 4), chronic slope (week 4 to month 12) and total slope using a spline mixed effects repeated measures model on the entire cohort and in the following baseline subgroups – eGFR <30, 30 to <45, ≥45 ml/min/1.73m²; A1, A2 and A3 albuminuria; glycated hemoglobin A1C <8%, ≥8 to <9%, ≥9%.

Results

Within the entire cohort of 10,574 participants, a placebo-adjusted acute decline in eGFR of -2.59 ml/min/1.73m²/year (95% CI -2.88, -2.30; p<0.0001) was observed. The chronic slope, measured after this acute decline, was 1.99 ml/min/1.73m²/year in favor of SOTA (95% CI 1.63, 2.34; p<0.0001). The total placebo-adjusted slope was -0.08 ml/min/1.73m²/year (95% CI -0.43, 0.27; p=0.67). The magnitude of the acute decline attenuated across progressively lower eGFR subgroups (P-interaction =0.017). Effects on chronic slope were consistent across baseline eGFR and A1C subgroups (P-interaction=0.48 and 0.22). Compared to placebo, SOTA had a greater benefit on chronic slope with increasing baseline albuminuria (P-interaction=0.023)

Conclusion

In participants with DKD, treatment with SOTA conferred kidney protection across a spectrum of baseline kidney function and glycemic control. The magnitude of kidney protection was larger with increasing albuminuria.

Funding

• Commercial Support – Lexicon Pharmaceuticals