The SMART trial, presented at Kidney Week 2024 and published in Nature Medicine, reveals that semaglutide (Ozempic/Wegovy) significantly reduces albuminuria in patients with chronic kidney disease (CKD) and obesity who do not have diabetes. The placebo-controlled, double-blind trial evaluated semaglutide 2.4 mg in this patient population, with the primary outcome being the change in urine albumin-to-creatinine ratio (UACR) at week 24.
The trial enrolled 101 patients aged 18 to 75 with CKD (eGFR ≥25 mL/min/1.73m²) and a BMI ≥27 kg/m². Baseline characteristics included a mean Cr-eGFR of 65 mL/min/1.73m², median UACR of 251 mg/g, mean BMI of 36.2 kg/m², and prevalent ACE inhibitor or ARB use (87%).
Key Findings from the SMART Trial
Results showed a placebo-corrected UACR reduction of -52.1% (95% CI, -65.2 to -34.1; P <.0001) in the semaglutide arm by week 24, with effects sustaining 4 weeks post-treatment. While there was an initial decline in Cr-eGFR by week 8, no significant Cr-eGFR difference was observed between groups at week 24 (mean difference, -1.1 mL/min/1.73m²; P = .57). Secondary outcomes included body weight and waist circumference reductions of -9.1 kg (P <.0001) and -4.4 kg (P = .04), respectively. Researchers observed no correlation between weight and eGFR changes.
Implications for CKD Treatment
Hiddo Heerspink, PhD, PharmD, of the University of Groningen, who presented the SMART trial, explained the rationale behind the study, noting that the pandemic lockdowns provided an opportunity to explore semaglutide's application for CKD without diabetes. The findings suggest that semaglutide's benefits extend beyond diabetes management, potentially offering a new therapeutic avenue for kidney and cardiovascular care. The study also explored dose-dependency, suggesting that higher doses may amplify albuminuria reduction, and the relationship between creatinine and cystatin C as filtration markers.
The results underscore semaglutide’s versatility, suggesting new therapeutic avenues across kidney and cardiovascular care. Future research will focus on additional trials to clarify semaglutide’s role in non-diabetic CKD and broader nephrology applications.
