Semaglutide, a GLP-1 receptor agonist, demonstrates promise in managing chronic kidney disease (CKD) in patients without diabetes. A recent study presented at the American Society of Nephrology’s Kidney Week 2024 and published in Nature, reveals that semaglutide significantly reduces albuminuria in obese patients with non-diabetic CKD.
The investigator-initiated, placebo-controlled, double-blind clinical trial evaluated the safety and efficacy of semaglutide 2.4 mg in patients with obesity and non-diabetic CKD. The primary outcome was the change in urine albumin-to-creatinine ratio (UACR) at week 24.
Study Design and Patient Population
The trial enrolled 101 patients aged 18 to 75 years with CKD, defined as an eGFR of at least 25 mL/min/1.73m2 and a UACR of 30 to 3500 mg/g, and a body mass index of at least 27 kg/m2. Participants were randomized to receive either semaglutide (n=51) or placebo (n=50). The mean age of the cohort was 56 years, 40% were female, and 91% were White. Baseline characteristics included a mean eGFR of 65 mL/min/1.73m2, a median UACR of 251 mg/g, and a mean BMI of 36.2 kg/m2.
The most common kidney disease diagnoses were chronic glomerulonephritis (25%) and hypertensive nephropathy (27%). A significant proportion of the cohort (87%) were using ACE inhibitors or ARBs, and 19% were on SGLT2 inhibitors.
Significant Reduction in Albuminuria
Results indicated that the geometric mean percentage change from baseline in UACR at week 24 was 7.4% (95% CI, -8.7 to 26.2) in the placebo group. In contrast, the semaglutide group experienced a geometric mean percentage change from baseline of -48.6% (95% CI, -60.9 to -32.3), resulting in a placebo-corrected geometric mean change of -52.1% (95% CI, -65.2 to -34.1; P < .0001).
The reduction in UACR was observed at each up-titration step of semaglutide, with the full effect evident at week 20, five weeks after reaching the 2.4 mg once-weekly dose. This effect was sustained until week 24 and remained present four weeks after discontinuing semaglutide.
Secondary Outcomes and Safety
No statistically significant difference in Cr-eGFR was observed between the semaglutide and placebo groups at week 24 (mean difference, -1.1 mL/min/1.73m2; 95% CI, -4.8 to 2.6; P = .57). An initial decrease in Cr-eGFR was noted at week 8 in the semaglutide group, but values returned to baseline by week 24.
Semaglutide was associated with placebo-corrected changes from baseline in body weight and waist circumference of -9.1 kg (95% CI -11.0 to -7.2; P <.0001) and -4.4 kg (95% CI -8.4 to -0.3; P = .04), respectively, at week 24. No correlations were found between changes in body weight and eGFR during the 24-week treatment period.
Expert Commentary
According to Hiddo J.L. Heerspink, PhD, PharmD, of University Medical Center Groningen, "6 months’ treatment with semaglutide at 2.4 mg per week reduced albuminuria, improved blood pressure control, reduced body weight and body circumference in patients with CKD and obesity."
He also noted that “Future studies are needed to assess the long-term efficacy and safety of semaglutide in reducing the risk of kidney failure in these patients."
