A recent randomized trial has revealed that semaglutide, marketed as Wegovy, significantly reduces albuminuria in patients with chronic kidney disease (CKD) who do not have type 2 diabetes. The study, presented by Hiddo J.L. Heerspink, PhD, from University Medical Center Groningen, showed that a 24-week course of semaglutide at a dosage of 2.4 mg led to a remarkable 52.1% reduction in the urine albumin-to-creatinine ratio (UACR) compared to a placebo group.
Study Overview
The trial, known as SMART, included 101 patients, with 51 receiving semaglutide and 50 receiving a placebo. Participants had a mean age of 56, a body mass index (BMI) of 36.2, and an average estimated glomerular filtration rate (eGFR) of 65 mL/min/1.73 m². The reduction in UACR was sustained throughout a 4-week washout period, indicating lasting benefits of the medication.
Heerspink noted that the albuminuria reduction was consistent across various subgroups, including different baseline HbA1c levels, BMI categories, and UACR levels. However, significance was noted primarily in patients not taking sodium-glucose cotransporter-2 (SGLT2) inhibitors.
Impact on Kidney Function
Despite the positive effects on albuminuria, semaglutide did not demonstrate a significant impact on eGFR after 24 weeks. While there was a slight decrease in eGFR at week 8 (mean difference compared to placebo: -4.3 mL/min/1.73m²), levels normalized by week 24, with no observed changes in cystatin C-estimated eGFR or iohexol-measured GFR.
The lack of correlation between weight loss and changes in eGFR suggests that the degree of weight loss in this study might have been insufficient to yield a noticeable impact on kidney function. Heerspink mentioned that previous studies involving other GLP-1 receptor agonists, like tirzepatide, also lacked this correlation.
Metabolic Benefits and Side Effects
Participants receiving semaglutide also experienced significant metabolic improvements, including:
Body weight reduction: 20.1 lb (P<0.0001)
Waist circumference decrease: 4.4 cm (P=0.04)
Reduction in high-sensitivity C-reactive protein levels: 37.9% (P=0.01)
Systolic blood pressure drop: 6.3 mm Hg (P=0.01)
As expected with GLP-1 receptor agonists, semaglutide was associated with higher rates of gastrointestinal side effects, such as nausea (31.4% vs 4% in the placebo group), diarrhea (21.6% vs 4%), and constipation (15.7% vs 8%). Rates of serious adverse events were comparable between the two groups.
Conclusion and Future Directions
Heerspink emphasized the need for larger and longer studies focusing on CKD patients using semaglutide. The findings from this trial contribute to the growing body of evidence supporting the renal benefits of semaglutide, particularly in non-diabetic populations.
When asked about the potential for testing semaglutide in lower BMI patients with CKD without diabetes, Heerspink expressed strong support but cautioned against its use in individuals with excessively low BMI due to the weight-loss effects of the drug.
The results, published in Nature Medicine, highlight the potential of semaglutide as a therapeutic option for reducing albuminuria in patients with CKD, although further research is necessary to fully understand its impact on kidney function and broader metabolic outcomes.
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