Semaglutide lowers UACR in overweight CKD patients

Study reveals semaglutide’s potential in lowering elevated urine albumin levels in overweight chronic kidney disease patients.

Study: Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial. Image Credit: crystal light / Shutterstock.com

In a recent study published in Nature Medicine, researchers investigate the clinical efficacy of semaglutide in controlling excessively high urine albumin-to-creatinine ratio (UACR) among overweight patients with chronic kidney disease (CKD).

How does obesity affect kidney function?

Overweight and obesity are some of the most prevalent chronic conditions plaguing individuals throughout the world, with an estimated two billion individuals living with these diseases globally.

Excessive body weight significantly increases the risk of other potentially lethal chronic diseases, including diabetes, cancers, and cardiovascular diseases (CVDs). High body mass index (BMI) can also disrupt kidney function through non-diabetes-related pathophysiological mechanisms such as hemodynamic perturbations. This can lead to hyperfiltration, enhanced intra-glomerular 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 managing CKD in some patients. However, a subset of patients, particularly those presenting with albuminuria, remain unresponsive to current therapies, thus emphasizing the need for novel treatments that can simultaneously address both body weight and albuminuria concerns.

About the study

The current study investigates the efficacy of weekly semaglutide interventions for six weeks in effectively managing UACR concentrations in overweight or obese patients diagnosed with CKD but without medically diagnosed diabetes. Semaglutide is a relatively novel glucagon-like peptide-1 (GLP-1) receptor agonist that is currently approved to treat diabetes and promote weight loss in overweight and obese individuals.

The study involved a double-blind, placebo-controlled, multicenter, parallel clinical trial conducted across 14 locations in four countries including Spain, Canada, the Netherlands, and Germany. Adults 18 years of age and older with clinically diagnosed CKD, BMI values exceeding 27 kg/m², and UACR between 30-3,500 mg/g were screened for study inclusion. Any individual with diabetes, hemoglobin A1c (HbA1c) levels exceeding 6.5%, or recent CVD events were excluded.

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

All treatments were administered at study centers by trained investigators. During each visit, body weight, heart rate, waist circumference, and blood pressure measurements were also obtained.

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

Study findings

A total of 101 individuals, 40% of whom were female, were included in the study. During the 28-week-long trial, one participant from both cohorts discontinued due to adverse reactions. Four participants in both groups also discontinued for personal reasons, leaving a final cohort size of 46 cases and 45 controls.

The most common CKD diagnoses among the study participants included chronic glomerulonephritis and hypertensive nephropathy, which were present in 25% and 27% of the study cohort, respectively. The mean BMI of the study participants was 36.3 kg/m², whereas the mean UACR was 251 mg/g.

Semaglutide treatment had a significant impact on UACR concentrations, with cases exhibiting a 48.6% reduction from their baseline values by week 24. This represents a 52.1% improvement as compared to controls.

Similar improvements in albumin concentrations were observed, as semaglutide recipients exhibited 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 semaglutide treatment was generally well-tolerated, some side effects were reported, the most common of which included nausea and diarrhea. Hypoglycemia was also observed in two individuals in the placebo group and one semaglutide recipient.

Conclusions

Semaglutide treatment 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 implicated in CVD events.

The effects of semaglutide were retained even during the 28-week follow-up evaluation, thus 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 kidney failure and cardiovascular complications in these patients.”