Summary: In a decentralized, double-blind, placebo-controlled n-of-1 crossover trial of 20 adults with type 2 diabetes and albuminuria, dapagliflozin 10 mg daily reduced the urine albumin-to-creatinine ratio (UACR) by 15.1% versus placebo (95% CI, -28.2% to -3.3%; P=.01) across 1-week treatment periods. Remote sample collection was shown to be feasible and reliable.
PICO Summary
| Element | Detail |
|---|---|
| Population | 20 adults with type 2 diabetes, UACR >20 mg/g, and eGFR >30 mL/min/1.73 m2; mean age 64.9 years, 85% male; decentralized trial in the Netherlands (n-of-1 design). |
| Intervention | Dapagliflozin 10 mg once daily, given in two 1-week periods per participant with 1-week washouts (within-subject crossover). |
| Comparison | Matched placebo, given in two 1-week periods per participant in random order (within-subject comparison). |
| Outcome | Relative UACR change with dapagliflozin versus placebo of -15.1% (95% CI, -28.2% to -3.3%; P=.01). Responses correlated between repeat dapagliflozin exposures (r=0.50; P=.03) but not placebo (r=0.09; P=.69). Remote data collection: 811/816 urine (99.4%) and 433/440 blood (98.4%) samples delivered. No hard renal or cardiovascular outcomes were assessed. |
Dapagliflozin and Albuminuria Response
N-of-1 crossover RCT · type 2 diabetes · 1-week periods
Within-subject dapagliflozin lowered UACR by 15.1% vs placebo with reproducible individual responses, but this n-of-1 proof-of-method study used a 1-week surrogate endpoint and no hard outcomes.
Expert Commentary
This small crossover trial is best read as a proof-of-method study rather than evidence of clinical benefit. A within-subject UACR reduction of 15.1% versus placebo is consistent with the known pharmacology of SGLT2 inhibition, and the correlation between repeat dapagliflozin exposures suggests individual response is reproducible, whereas placebo periods were not. Equally notable is the demonstration that decentralized, remote sampling can be performed reliably, with almost all specimens delivered to the central laboratory. The principal limitation is scale and horizon: only 20 participants were studied over 1-week periods, with a surrogate endpoint and no assessment of hard renal or cardiovascular outcomes, so durability and clinical translation remain unproven. Can I use this with my patients? Not yet as a basis for individualised dapagliflozin decisions; the established indication for SGLT2 inhibitors in diabetic kidney disease rests on large outcome trials, and this work informs methodology rather than prescribing. The findings should encourage further n-of-1 and decentralized designs to identify responders prospectively. Because dapagliflozin is a marketed product, replication in independent, adequately powered cohorts with longer follow-up would strengthen confidence before response-guided dosing is considered in routine practice.
References
Beernink JM, Jongs N, Doelman CJA, Laverman GD, Heerspink HJL. Albuminuria Responses to Dapagliflozin in Patients With Type 2 Diabetes: A Crossover Trial. JAMA Netw Open. 2025;8(3):e251689. doi:10.1001/jamanetworkopen.2025.1689