Albuminuria Responses to Dapagliflozin in Patients With Type 2 Diabetes: A Crossover Trial.

Importance: Dapagliflozin reduces the urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) decline at a population level, but individuals show a large variation in responses. The n-of-1 trial design allows for direct assessment of treatment effects within an individual, and digital technologies and remote study assessments can reduce clinic visits, ease participant burden, and improve trial efficiency. Objective: To assess individual UACR responses to dapagliflozin treatment in a decentralized clinical trial and the feasibility of remote data collection. Design, Setting, and Participants: This decentralized, randomized, double-blind, placebo-controlled crossover trial using an n-of-1 approach was conducted using data from the Dutch primary and secondary health care systems between May 2021 and September 2022. Participants included adults with type 2 diabetes, a UACR greater than 20 mg/g, and an eGFR greater than 30 mL/min/1.73 m2. Statistical analyses were performed between June and August 2023. Interventions: Participants were assigned to two 1-week treatment periods with dapagliflozin, 10 mg/d, and two 1-week treatment periods with placebo in random order, with 1-week washout periods in between. Main Outcomes and Measures: The primary outcome was the difference in the change in UACR from start to end of treatment between dapagliflozin and placebo in the per-protocol population. A post hoc exploratory analysis assessed the feasibility of remote data collection, including the proportion of urine and capillary blood samples successfully delivered to the central laboratory. Results: In total, 20 participants (mean [SD] age, 64.9 [8.7] years; 17 [85.0%] male) with a mean (SD) eGFR of 70.2 (20.3) mL/min/1.73 m2 and a median UACR of 94.7 (IQR, 29.8-242.6) mg/g were included in the study. They experienced a relative change in UACR with dapagliflozin compared with placebo of -15.1% (95% CI, -28.2% to -3.3%; P = .01). UACR changes showed considerable variation during both dapagliflozin and placebo treatment (first treatment period: median, -12.8% [range, -56.3% to 36.2%] and 2.9% [range, -86.7% to 35.1%], respectively). UACR changes correlated significantly between the first and second dapagliflozin exposure (r = 0.50; P = .03), with no correlation observed between the placebo exposure periods (r = 0.09; P = .69). With regard to remote data collection, 811 of 816 urine samples (99.4%) and 433 of 440 capillary blood samples (98.4%) were successfully delivered to the central laboratory. Conclusions and Relevance: In this crossover trial, individual UACR responses to dapagliflozin reflected a pharmacological response. Remote data collection proved to be reliable, supporting its use in future studies and clinical practice for monitoring individual dapagliflozin responses. Trial Registration: EudraCT identifier: 2020-004929-23.