Jelle M. Beernink¹, Niels Jongs¹, Cees J.A. Doelman², Gozewijn D. Laverman^3,4, Hiddo J.L. Heerspink¹

1. Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, the Netherlands; 2. Department of Clinical Chemistry, Medlon Laboratory Diagnostics, Unilabs, Enschede, the Netherlands; 3. Department of Internal Medicine / Nephrology, Ziekenhuis Groep Twente, Almelo, the Netherlands; 4. Biomedical Signals and Systems (BSS), University of Twente, Enschede, the Netherlands.

E-mail address presenting (first) author: j.m.beernink@umcg.nl

Background: The Sodium Glucose Cotransporter 2 (SGLT2) inhibitor dapagliflozin reduces urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) decline in patients with chronic kidney disease. However, there is marked heterogeneity in the efficacy among individual patients. We conducted a series of decentralized N-of-1 trials to assess the effect of dapagliflozin in individual patients and the feasibility of remote data collection.

Methods: Adults with type 2 diabetes, UACR 20 mg/g, and eGFR 30 mL/min/1.73m² were enrolled in a series of randomized, placebo-controlled, double-blind N-of-1 trials (NCT06374043). Participants were assigned to one-week treatment periods with dapagliflozin 10 mg/day and placebo in random order, with one-week wash-out periods in between. Participants collected and sent their own data via an online platform and mailed urine and blood samples to a central lab. The primary outcome was UACR change from baseline.

Results: 20 participants (mean age 64.9 year, 3 females, mean eGFR 70.2 mL/min/1.73m², and median UACR 94.7 mg/g) were enrolled into the study. Geometric mean change from baseline in UACR with dapagliflozin compared to placebo was -15.1% (95% CI -28.2, -3.3; P = 0.013). There was marked variation in UACR change during both dapagliflozin and placebo treatment (range first dapagliflozin and placebo treatment period -56.3% to 36.2%, and -86.7% to 35.1%, respectively). The individual UACR change during the first and second dapagliflozin exposure correlated significantly (r = 0.50; P = 0.026) but no correlation was seen during placebo exposure periods (r = 0.09; P = 0.69). Of all scheduled urine collections (N = 816), 811 (99.4%) were delivered in the laboratory.

Conclusion: The individual UACR response to dapagliflozin varies among individual patients and is consistent upon re-exposure. Remote data collection was very reliable, supporting the implementation of remote data collection in future studies and clinical practice to monitor individual dapagliflozin response.