Semaglutide and the Future of Kidney Disease, with Brendon Neuen, MBBS, PhD

The rise of semaglutide (Ozempic, Wegovy) is a phenomenon unlike any other witnessed in modern healthcare. Outside of vaccinations, there are few examples of agents commanding the same level of attention as the GLP-1 receptor agonist, which has captured the eye of both the medical community and general public alike with its promise of weight loss, cardiovascular, and, now, kidney benefits.^1,2,3

Semaglutide, and the GLP-1 receptor agonist class as a whole, has distanced itself from previous notions suggesting its role was solely for improving glucose control. Among the public, this was driven by results of trials purporting historic benefits in weight loss, which led to approvals for weight management.¹

Next, semaglutide captivated the general public and medical community alike with revelations of its cardiovascular benefits among patients with overweight or obesity and a history of cardiovascular disease without diabetes. This trial, which examined the 2.4 mg dose of semaglutide, was used as the basis of a first-of-its-kind indication from the US Food and Drug Administration in March 2024.²

At the 61st European Renal Association Conference, the latest landmark trial offered evidence that could lead to an additional label expansion from the FDA: the FLOW trial. The trial, which was stopped early due to efficacy, examined use of the 1.0 mg dose of semaglutide for kidney outcomes in patients with type 2 diabetes at risk for chronic kidney disease—the first GLP-1 receptor agonist trial to do so.³

The trial concluded use of semaglutide 1.0 mg was associated with a 24% relative risk reduction for a composite endpoint of dialysis, transplantation, an eGFR decline to less than 15 ml/min/1.73m2, a reduction of 50% or greater in eGFR from baseline, or death from kidney-related or cardiovascular causes. Secondary endpoint analyses from the trial also garnered considerable attention, including a statistically significant 20% reduction in all-cause mortality.³

The overlap between the fields extends not only to therapies, but also evolutions in conceptual approach to management with many in nephrology now advocating for a pillared approach to chronic kidney disease management, much like the field of heart failure has adopted in recent years.

With interest in the evolving landscape of chronic kidney disease, the cardiorenal protective effects of GLP-1 receptor agonist therapies, and other updates from the world of nephrology, Don’t Miss a Beat hosts Muthiah Vaduganathan, MD, MPH, co-director of the Center for Cardiometabolic Implementation Science at Brigham and Women’s Hospital, and Steve Greene, MD, advanced heart failure specialist at the Duke Clinical Research Institute, sit down with Brendon Neuen, MBBS, PhD, nephrologist and director of the Kidney Trials Unit at Royal North Shore Hospital and senior research fellow at The George Institute for Global Health.

Relevant disclosures for Vaduganathan include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others. Relevant disclosures for Greene include Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others. Relevant disclosures for Neuen include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others.

References:

1. Campbell P. Semaglutide (Wegovy) approved for chronic weight management in patients with obesity or overweight. HCP Live. April 17, 2023. Accessed May 29, 2024. https://www.hcplive.com/view/semaglutide-approved-for-chronic-weight-management-in-patients-with-obesity-or-overweight.
2. Campbell P. Semaglutide (Wegovy) receives FDA label expansion to include cardiovascular risk reduction. HCP Live. March 8, 2024. Accessed May 29, 2024. https://www.hcplive.com/view/semaglutide-wegovy-receives-fda-label-expansion-to-include-cardiovascular-risk-reduction.
3. Campbell P. Flow trial fortifies SEMAGLUTIDE’s role in chronic kidney disease and type 2 diabetes. HCP Live. May 24, 2024. Accessed May 29, 2024. https://www.hcplive.com/view/flow-trial-fortifies-semaglutide-s-role-in-chronic-kidney-disease-and-type-2-diabetes.