Semaglutide reduces UACR in overweight CKD patients

Study reveals semaglutide‘s potential in reducing elevated urinary albumin levels in overweight chronic kidney disease patients.

Study: Semaglutide in overweight or obese patients with chronic kidney disease without diabetes: a randomized double-blind, placebo-controlled clinical trial. Image credits: crystallight / Shutterstock.com

From a recent study published in Naturopathy, researchers are investigating the clinical efficacy of semaglutide in controlling high urinary albumin-to-creatinine ratio (UACR) in overweight patients with chronic kidney disease (CKD).

How does obesity affect kidney function?

Overweight and obesity are some of the most common chronic conditions affecting people around the world, with an estimated two billion people worldwide living with these diseases.

Excess body weight significantly increases the risk of other potentially fatal chronic diseases, including diabetes, cancer and cardiovascular disease (CVD). High body mass index (BMI) may also impair renal function via non-diabetes-related pathophysiological mechanisms such as hemodynamic disturbances. This can lead to hyperfiltration, increased intraglomerular pressure, inflammation and increased oxidative stress.

Conventional anti-CKD interventions often include sodium-glucose co-transporter 2 (SGLT2) inhibitors and renin-angiotensin system (RAS) inhibitors, which can effectively treat CKD in some patients. However, a subset of patients, especially those presenting with albuminuria, still do not respond to current therapies, highlighting the need for new treatments that can simultaneously address both body weight and albuminuria problems.

About the study

The current study examines the efficacy of weekly semaglutide interventions for six weeks in effectively controlling UACR concentrations in overweight or obese patients diagnosed with chronic kidney disease but without medically diagnosed diabetes. Semaglutide is a relatively new glucagon-like peptide-1 (GLP-1) receptor agonist currently approved for the treatment of diabetes and promotion of weight loss in overweight and obese individuals.

The study involved a double-blind, placebo-controlled, multi-center, parallel clinical trial conducted at 14 sites in four countries, including Spain, Canada, the Netherlands and Germany. Adults aged 18 years and over with clinically diagnosed chronic kidney disease, BMI values ​​greater than 27 kg/m2²and UACR between 30-3,500 mg/g were screened for inclusion in the study. Anyone with diabetes, a hemoglobin A1c (HbA1c) level greater than 6.5%, or recent CVD events were excluded.

Study participants were randomly assigned to receive a 2.4 mg subcutaneous injection of semaglutide once weekly or an equivalent placebo. In the semaglutide cohort, the initial injection dose was 0.25 mg/week and was gradually increased to 0.5, 1.0, 1.7, and 2.4 mg at weeks four, eight, 12, and 16, respectively. The experiment was continued for Conducted for 24 weeks, followed by a four-week washout period for further data collection and monitoring of participants.

All treatments were administered at study centers by trained researchers. Measurements of body weight, heart rate, waist circumference, and blood pressure were also taken during each visit.

Urinary creatine and albumin concentrations were recorded daily using first morning urine samples. Glomerular filtration rates (GFRs) were measured using plasma clearance of non-radioactive iohexol assays performed three times to determine estimated GFR (eGFR) values ​​via the CKD Epidemiology Collaboration equation.

Findings of the study

A total of 101 people, 40% of whom were women, were included in the study. During the 28-week trial, one participant from both cohorts dropped out due to side effects. Four participants in both groups also dropped out for personal reasons, leaving a final cohort size of 46 cases and 45 controls.

The most common CKD diagnoses among study participants were chronic glomerulonephritis and hypertensive nephropathy, which were present in 25% and 27% of the study cohort, respectively. The average BMI of the study participants was 36.3 kg/m2²while the mean UACR was 251 mg/g.

Semaglutide treatment had a significant impact on UACR concentrations, with cases showing a 48.6% decrease from baseline at week 24. This represents an improvement of 52.1% compared to the control group.

Similar improvements in albumin concentrations were observed, as semaglutide recipients showed 41.6% lower levels than controls. Notably, these findings were consistent across all subgroups. Semaglutide treatment also improved N-terminal pro-B-type natriuretic peptide (NT-proBNP) and HbA1c concentrations by 31.9% and 0.35%, respectively.

Although treatment with semaglutide was generally well tolerated, some side effects were reported, the most common of which were nausea and diarrhea. Hypoglycemia was also observed in two subjects in the placebo group and in one semaglutide recipient.

Conclusions

Treatment with semaglutide led to a 52% reduction in UACR levels in non-diabetic and overweight patients diagnosed with CKD. Furthermore, semaglutide led to improvements in NT-proBNP and HbA1c levels, both of which are involved in CVD events.

The effects of semaglutide were maintained even during the 28-week follow-up evaluation, suggesting the need to investigate the potential long-term benefits of semaglutide treatment.

These findings support future clinical trials to assess the efficacy of semaglutide in reducing the risk of renal failure and cardiovascular complications in these patients.”