SELECT trial shows semaglutide reduces kidney decline in obese patients

The SELECT Trial has revealed the potential of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in combating kidney function decline among individuals with overweight or obesity and established cardiovascular disease but without diabetes.

Unveiling the results today at the 61st ERA Congress, researchers presented the impressive secondary analysis from the SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity) trial, a randomized trial comprising a participant pool of 17,604 individuals.

Experts believe the study's results offer hope for those affected by obesity, a condition known to exacerbate the risk of kidney function decline and macroalbuminuria (abnormal amounts of the albumin protein in urine).

With an average follow-up of approximately 3.5 years, among patients who were administered a once-weekly subcutaneous injection of semaglutide 2.4 mg (n=8,803) adverse kidney-related events were experienced by 22% fewer persons (1.8%) compared to those receiving placebo (n=8,801) (2.2%) (p<0.05). These events included death from kidney causes, initiation of chronic kidney replacement therapy, significant (≥ 50%) decline in kidney function, or onset of persistent macroalbuminuria. Semaglutide's ability to prevent the onset of macroalbuminuria was highlighted as a pivotal factor in reducing the likelihood of kidney-related complications.

The study also assessed the impact of semaglutide on estimated glomerular filtration rate (eGFR), a measure of kidney function in removing waste and excess water from the blood through urine. The findings indicated a significantly lesser decline in eGFR among semaglutide recipients compared to the placebo group, with the effect being more pronounced in participants with baseline eGFR below 60 mL/min/1.73 m² (p<0.001). These results indicate the potential for semaglutide to particularly protect kidney function in individuals with a pre-existing kidney impairment.

The reduction in urinary albumin-to-creatinine ratio (UACR) further substantiated semaglutide's beneficial effect on kidney health, with a significant decrease observed in semaglutide-treated individuals compared to placebo (p<0.001). UACR analysis measures the ratio of albumin (a protein) to creatinine (a waste product) in urine, aiding the detection of albuminuria, which can signal kidney damage or dysfunction. With semaglutide, there was a net 8.1% decrease in UACR in those with normal albumin levels at baseline, a 27.2% decrease in those with microalbuminuria (slightly raised albumin) at baseline, and a 31.4% decrease in those with macroalbuminuria at baseline relative to placebo.

Importantly, the study found no increased risk of acute kidney injury associated with semaglutide treatment, irrespective of baseline kidney function.

Over one billion people worldwide are affected by obesity. Rates of obesity are rising significantly, having doubled among adult women (8.8% to 18.5%) and nearly tripled in adult men (4.8% to 14.0%) between 1990 and 2022. The total number of children affected by obesity in 2022 was nearly 160 million, compared to 31 million in 1990.

By addressing key markers of kidney health, semaglutide 2.4 mg weekly may contribute to a significant reduction in the risk of kidney-related complications, including chronic kidney disease and end-stage renal disease. This could lead to improved management of comorbidities and, ultimately, enhance the quality of life for individuals with obesity."

The observed benefits in eGFR and UACR are particularly encouraging, suggesting potential for the enhanced management of kidney complications in the patient population with overweight and obesity without diabetes. The findings also underscore the importance of continued research into the possible renal benefits of semaglutide and highlight its role as a promising therapeutic option in the multifaceted management of cardiovascular and renal health in this high-risk population."

Professor Helen M. Colhoun, lead study author

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