Diabetes Dialogue: FLOW Trial and Chronic Kidney Disease Updates, with Brendon Neuen, MBBS, PhD

The management of glomerular disease looks entirely different now than it did at the turn of the century. For decades, the most common strategy for management of chronic kidney disease (CKD) in patients with type 2 diabetes was RAAS blockade and watchful waiting as kidney function declined.

In 2024, this is no longer case. Driven primarily by pharmacologic advances in the past 15 years, the ability of clinicians to manage declining kidney function among people with diabetes has undergone a revolution. In the last half-decade, the community has seen agents from the SGLT2 inhibitor and nonsteroidal mineralocorticoid receptor agonist classes showcase benefit in clinical trial programs and gain subsequent approval.

In March 2024, the medical community received information that could further change management to CKD in people with diabetes, with the announcement of topline results from the FLOW trial. A placebo-controlled trial with more than 3500 patients with type 2 diabetes and CKD, the FLOW trial compared semaglutide 1.0 (Ozempic) against placebo and found use reduced risk of a composite endpoint of worsening kidney function by 24%.

Launched in 2019, the trial included patients with eGFR of ≥50 and ≤75mL/min/1.73 m2 and UACR >300 and <5000 mg/g or eGFR ≥25 and <50 mL/min/1.73 m2 and UACR >100 and <5000 mg/g. The primary outcome of interest was a composite of the 5 following endpoints:

• Onset of persistent ≥ 50% reduction in eGFR according to the CKD-EPI3 equation compared with baseline,
• Onset of persistent eGFR (CKD-EPI) < 15 mL/min/1.73 m2
• Initiation of chronic kidney replacement therapy (dialysis or kidney transplantation)
• Death from kidney disease
• Death from cardiovascular disease

According to their March 05, 2024, announcement, Novo Nordisk intends to file for regulatory approvals of a label expansion for Ozempic in the US and the European Union in 2024. Later in March, Novo Nordisk announced its intent to present full results at the upcoming European Renal Association meeting.

In this episode of Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, are joined by 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. During the episode, Neuen talks about the FLOW trial, topline results, how the rapid advancement in pharmacotherapies have altered conversations around management, the concept of 4 pillars of GDMT for CKD in type 2 diabetes, and how to approach sequencing of these therapies.

Relevant disclosures for Dr. Neuen include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others. Relevant disclosures for Dr. Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Dr. Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.

References:

1. Campbell P. Finerenone (Kerendia) approved for chronic kidney disease associated with type 2 diabetes. HCP Live. July 9, 2021. Accessed March 21, 2024. https://www.hcplive.com/view/finerenone-kerendia-approved-chronic-kidney-disease-associated-with-type-2-diabetes.
2. Campbell P. Semaglutide 1.0 mg (ozempic) reduced kidney events 24% in flow trial. HCP Live. March 5, 2024. Accessed March 21, 2024. https://www.hcplive.com/view/semaglutide-1-0-mg-ozempic-reduced-kidney-events-24-in-flow-trial.
3. Campbell P. Empagliflozin (Jardiance) Receives CKD Approval from US FDA. HCPLive. September 22, 2023. Accessed March 20, 2024. https://www.hcplive.com/view/empagliflozin-jardiance-receives-ckd-approval-from-us-fda.