How T2D Patients With Albuminuria Respond to Dapagliflozin?

TOPLINE: 

In patients with type 2 diabetes (T2D) and albuminuria, compared with placebo, dapagliflozin reduced the urine albumin-to-creatinine ratio (UACR) by 15.1%, with a considerable variation in individual responses. These variations in the UACR were observed consistently upon re-exposure to dapagliflozin.

METHODOLOGY:

• Researchers conducted a decentralised crossover trial to examine individual responses to dapagliflozin, a selective sodium-glucose cotransporter 2 inhibitor, among patients with T2D and albuminuria.
• They included 20 adults (mean age, 64.9 years; 15% women) who had T2D, a UACR > 20 mg/g, and an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m²; all participants were on a stable dose of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker.
• Participants completed two 1-week treatment periods with dapagliflozin (10 mg/day) and two 1-week treatment periods with placebo, in random order, separated by 1-week washout periods to prevent carryover effects.
• Data for the study were collected remotely using digital devices, with participants providing daily first morning void urine samples and capillary blood samples; blood pressure and body weight were measured daily using connected devices.
• The primary outcome was the difference in UACR change from the start to the end of treatment between dapagliflozin and placebo in the per-protocol population; secondary outcomes included changes in blood pressure, body weight, eGFR, and fasting plasma glucose levels.

TAKEAWAY:

• Compared with placebo, dapagliflozin reduced albuminuria by 15.1% (P = .01).
• Individual responses to dapagliflozin varied widely, with UACR changes ranging from −56.3% to 36.2% (median, −12.8%) in the first period and −86.2% to 54.4% (median, −21.3%) in the second; a significant correlation in individual UACR changes between the first and second dapagliflozin periods was observed (correlation coefficient, 0.50; P = .03).
• Compared with placebo, dapagliflozin reduced systolic blood pressure by −5.11 mm Hg (P = .008), body weight by −0.53 kg (P < .001), and eGFR by −5.33 mL/min/1.73 m² (P = .03).
• Additionally, remote data collection was highly effective, with 99.4% of urine samples and 98.4% of capillary blood samples successfully collected and analysed.

IN PRACTICE:

“Dapagliflozin reduced UACR compared with placebo, although considerable variability was observed among individuals. These variations, which were consistent after re-exposure, underscore the need for personalised approaches to diabetes and CKD [chronic kidney disease] management,” the authors wrote.

“[The study findings] demonstrated that individual responses to these agents were highly heterogeneous. Thus, patients may benefit from a therapeutic regimen carefully tailored to their unique physiology,” experts wrote in an accompanying editorial.

SOURCE:

The study was led by Jelle M. Beernink, MD, University Medical Center Groningen, Groningen, the Netherlands, and was published online on March 24, 2025, in JAMA Network Open.

LIMITATIONS:

The study’s small sample size may have limited the generalisability of its findings. The short duration of dapagliflozin exposure was sufficient for detecting early effects but left uncertainty about the drug’s long-term outcomes. Additionally, remote data collection may be less feasible for individuals with limited technical skills or those in areas with unreliable internet infrastructure.

DISCLOSURES:

The study was funded by University Medical Center Groningen and supported by AstraZeneca, which provided the medication. Some authors reported receiving research grants, travel support, personal fees, or honoraria or having other ties with various pharmaceutical companies. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.