Kidney Week

Abstract: TH-OR079

Reproducibility of Placebo-Corrected Albuminuria Responses to Dapagliflozin in Type 2 Diabetes and CKD: Bayesian N-of-1 Trial Approach

Session Information

• Precision Medicine in Diabetic Kidney Disease: Biomarkers, Combination Therapies, and Treatment Response Prediction
  November 06, 2025 | Location: Room 372A, Convention Center
  Abstract Time: 05:30 PM - 05:40 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Beernink, Jelle, Universitair Medisch Centrum Groningen, Groningen, Netherlands

Jelle Beernink, MD

• Jongs, Niels, Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands

Niels Jongs, PhD

• Heerspink, Hiddo Jan L., Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands

Hiddo Jan L. Heerspink, PhD

Background

Patients with type 2 diabetes and CKD show a large between-individual variation in albuminuria responses to the SGLT2 inhibitor dapagliflozin. N-of-1 trials, in which individuals receive treatment and placebo repeatedly, allow for precise estimation of individual placebo-corrected effects and individual response reproducibility upon re-exposure. We developed a Bayesian model to assess if a participant’s initial placebo-corrected response predicts their response upon re-exposure.

Methods

We conducted a randomized, placebo-controlled n-of-1 trial in participants with type 2 diabetes and CKD. Each participant received dapagliflozin (DAPA) and placebo twice for one week in random order, enabling within-person estimation of placebo-corrected responses during the first and second exposure. Generalized pairwise comparisons yielded 3,160 within- and between-subject ΔUACR comparisons from baseline. Bayesian hierarchical models estimated the posterior UACR response using priors from each participant’s first exposure.

Results

Twenty participants (mean age 64.9 years, mean eGFR 70.2 mL/min/1.73m², median UACR 94.7 mg/g) were included. Observed placebo-corrected UACR responses to DAPA ranged from –73.4% to 89.3% during the first exposure and –155.0% to 91.9% during the second. Model-predicted placebo-corrected UACR responses during the second DAPA exposure, based on DAPA responses during the first exposure ranged from –70.3% to 62.2% and correlated strongly with observed placebo-corrected DAPA responses upon re-exposure (r=0.70, P<.001; Figure). Participants with initial UACR reductions <–30% or <–20% had high probabilities of repeating the response during re-exposure (75.8% and 86.6%, respectively), compared to 3.0% and 4.8% for those without such reductions.

Conclusion

Placebo-corrected UACR responses to DAPA were reproducible and predictable, paving the way for individualized DAPA response monitoring.

Funding

• Commercial Support – AstraZeneca supported the study with study medication.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025m12tdzgx