Diabetes Dialogue: FLOW Trial and Semaglutide's Benefit in Chronic Kidney Disease

After years of anticipation, the FLOW trial has brought forth a conclusion many had expected but had no clinical trial data to prove: semaglutide 1.0 mg provides renoprotective benefit in patients with type 2 diabetes and chronic kidney disease (CKD).

With topline data announced in March 2024, the medical community waited with bated breath to learn about the full results of the trial, which were presented at the 61st European Renal Association Congress and offered insight into the effects beyond the trial’s primary composite endpoint by detailing the impact of semaglutide 1.0 mg across a myriad of kidney-specific and cardiovascular-based outcomes from the trial.

An international, double-blind, randomized, placebo-controlled trial, FLOW randomized 3533 patients in a 1:1 ratio to semaglutide 1.0 mg or placebo therapy. For inclusion in the trial, patients were required to have type 2 diabetes and chronic kidney disease, which was defined as an eGFR of 50 to 75 ml/min/1.73m2 of body-surface area and a UACR greater than 300 andless than5000 or an eGFR of 25 to less than 50 ml/min/1.73m2 and a UACR greater than 100 and less than 5000.

The trial’s primary outcome of interest was a composite of major kidney disease events, which included dialysis, transplantation, or an eGFR of less than15 ml/min/1.73m2, at least a 50% reduction in the eGFR from baseline, or death from kidney-related or cardiovascular causes.

Results suggested use of semaglutide was associated with a 24% relative risk reduction for the trial’s primary outcome of major kidney disease events compared to placebo therapy (Hazard Ratio [HR], 0.76; 95% Confidence Interval [CI], 0.66 to 0.88; P = .0003). Analysis of kidney-specific components of the primary outcome indicated semaglutide use was associated with a 21% reduction in risk relative to placebo therapy (HR, 0.79; 95% CI, 0.66 to 0.94). Further analysis demonstrated risk of death from cardiovascular causes was reduced by 29% relative to placebo therapy (HR, 0.71; 95% CI, 0.56 to 0.89).

To celebrate the trial and break down what it means for people with type 2 diabetes and CKD, 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, recorded a special edition episode of Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives. Check out the episode to learn more about the clinical application of this trial, unmet need in CKD management, the future of incretin therapies, and more!

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, Sanofi, and others.

References:

Perkovic V, Tuttle K, Rossing P, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. New England Journal of Medicine. Published online May 24, 2024. doi:10.1056/NEJMoa2403347