A recent study published in Nature Medicine examines the effectiveness of semaglutide in managing high urine albumin-to-creatinine ratio (UACR) among overweight patients with chronic kidney disease (CKD).
Impact of Obesity on Kidney Function
Obesity is a widespread health issue, affecting an estimated two billion people worldwide. Excess weight increases the risk of serious chronic conditions, including diabetes, cancer, and cardiovascular diseases (CVDs). Additionally, high body mass index (BMI) can impair kidney function through various mechanisms. These include changes in blood flow, increased pressure within the kidneys, inflammation, and higher oxidative stress.
Current treatments for CKD typically include sodium-glucose co-transporter 2 (SGLT2) inhibitors and renin-angiotensin system (RAS) inhibitors. While these medications can help some patients, many—especially those with albuminuria—do not respond to existing therapies. This highlights the need for new treatments that address both weight and albuminuria.
About the Study
The study tested the effectiveness of weekly semaglutide injections over six weeks to lower UACR levels in overweight or obese patients with CKD but without diabetes. Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for treating diabetes and aiding weight loss.
Researchers conducted a double-blind, placebo-controlled trial across 14 sites in Spain, Canada, the Netherlands, and Germany. Adults aged 18 and older, with a BMI over 27 kg/m² and UACR between 30-3,500 mg/g, were enrolled. Participants with diabetes, hemoglobin A1c (HbA1c) levels above 6.5%, or recent CVD events were excluded.
Participants were randomly assigned to receive either 2.4 mg of semaglutide or a placebo weekly. The semaglutide dosage started at 0.25 mg per week and was gradually increased. The trial lasted 24 weeks, followed by a four-week monitoring period.
During each visit, researchers recorded weight, heart rate, waist circumference, and blood pressure. Urinary creatinine and albumin levels were measured daily using morning samples. The study also assessed glomerular filtration rates (GFRs) through non-radioactive iohexol assays.
Study Results
The trial included 101 participants, with 40% being female. Throughout the study, one participant in each group dropped out due to adverse effects, while four others left for personal reasons, resulting in 46 in the semaglutide group and 45 in the placebo group.
The most common CKD diagnoses among participants were chronic glomerulonephritis and hypertensive nephropathy, affecting 25% and 27% of the group, respectively. The average BMI was 36.3 kg/m², and the mean UACR was 251 mg/g.
Participants treated with semaglutide saw a significant reduction in UACR, with levels dropping by 48.6% from their baseline by week 24. This marked a 52.1% improvement compared to the control group. Similar reductions in albumin levels were observed, with semaglutide recipients showing 41.6% lower levels than those on placebo. Improvements were consistent across all subgroups. Semaglutide also led to a 31.9% decrease in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and a 0.35% drop in HbA1c levels.
While semaglutide was generally well-tolerated, some participants reported side effects, with nausea and diarrhea being the most common. Two participants in the placebo group and one in the semaglutide group experienced hypoglycemia.
Conclusions
The study concluded that semaglutide significantly reduced UACR levels by 52% in overweight, non-diabetic patients with CKD. It also improved NT-proBNP and HbA1c levels, both of which are important for cardiovascular health. Notably, the benefits of semaglutide persisted during the follow-up, indicating a potential for long-term advantages that warrant further research.
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