SELECT Analysis: Semaglutide 2.4 mg (Wegovy) Reduces Negative Kidney Outcomes

Helen Colhoun, MD
Credit: University of Edinburgh

In addition to the cardiovascular risk reduction, an analysis of the landmark SELECT trial suggests use of semaglutide 2.4 mg (Wegovy) was associated with a reduction in kidney events as well.

Published on the heels of the FLOW trial, which examined the 1.0 mg dose of semaglutide, the analysis of the SELECT provides further evidence of the renoprotective effects of GLP-1 receptor agonists.¹

“So, this is important because this is a high-risk population and it's a population that needs renal protection,” explained Helen Colhoun, MD, professor of Medical Informatics and Epidemiology at University of Edinburgh, in an interview with HCPLive.¹ “Semaglutide can contribute to that renal protection, as well as achieving a reduction in major adverse cardiovascular endpoints.”

Presented at the American Heart Association’s 2023 Scientific Sessions, the SELECT trial assessed the efficacy and safety of semaglutide 2.4 mg relative to placebo therapy among patients with overweight/obesity and established cardiovascular disease but without diabetes. The trial included more than 16,000 patients and concluded use of semaglutide was associated with a 20% reduction in risk of major adverse cardiovascular events relative to placebo therapy among this cohort.^1,2

These data were used as the basis of an additional indication for the agent in reducing cardiovascular risk among patients with overweight or obesity with a history of cardiovascular disease, which was announced by Novo Nordisk in March 2024.²

Now, at the 61st European Renal Association (ERA 24) Congress, Colhoun presented additional data elucidating the agent’s effect on kidney-specific outcomes. The prespecified composite kidney outcome used in the analysis included death from kidney disease, initiation of chronic kidney replacement therapy, onset of persistent eGFR less than 15 ml/min/1.73m2, persistent reduction of 50% or more in eGFR, and onset of persistent macroalbuminuria.¹

In their manuscript, which was simultaneously published in Nature Medicine, investigators point out baseline characteristics were well balanced between treatment arms as it relates to kidney function and albuminuria status. Additionally, more than 20% of participants had an eGFR less than 60 ml/min/1.73m2 or a UACR of 30 mg/g or greater.¹

Over a median follow-up of 182 weeks, a primary outcome event occurred among 1.8% of the semaglutide group and 2.2% of the placebo group. The in-trial analysis suggested use of semaglutide was associated with a 22% relative reduction in risk of the primary outcome (HR, 0.78; 95% CI, 0.63 to 0.96; P = .02). The on-treatment analysis suggested use of semaglutide was associated with 25% relative reduction in risk of the primary outcome (HR, 0.75; 95% CI, 0.59 to 0.94; P = .01). Further analysis demonstrated this was driven primarily by a reduction in the onset of macroalbuminuria and persistent reduction of 50% or greater in eGFR.¹

The analysis also assessed the effect of semaglutide use on eGFR at 104 weeks, which suggested the relative benefit compared to placebo was 0.75 ml/min/1.73m2 (95% CI, 0.43 to 1.06; P < .001) overall and 2.19 ml/min/1.73m2 (95% CI, 1.00 to 3.38; P < .001) in patients with baseline eGFR less than 60 ml/min/1.73m2.¹

“I think it's important to really understand the extent and reach of the potential benefit of this on kidney disease because we've had very few renal protective drugs, really,” Colhoun added.

References:

1. Colhoun HM, Lingvay, I, Brown PM, et al. Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial. Nat Med. Published May 25, 2024. https://doi.org/10.1038/s41591-024-03015-5.
2. Campbell P. Semaglutide (Wegovy) receives FDA label expansion to include cardiovascular risk reduction. HCP Live. March 8, 2024. Accessed May 26, 2024. https://www.hcplive.com/view/semaglutide-wegovy-receives-fda-label-expansion-to-include-cardiovascular-risk-reduction.