Vlado Perkovic, MBBS, PhD: Semaglutide's Role in CKD Based on FLOW Results

As he took to the podium to present full efficacy results from the FLOW trial, Vlado Perkovic, MBBS, PhD, was greeted by a filled auditorium anxious for a glimpse into the future of chronic kidney disease management in people with type 2 diabetes.

For inclusion in semaglutide’s kidney outcomes trial, patients needed an eGFR of 50 to 75 ml/min/1.73m2 of body-surface area and a urinary albumin-to-creatinine ratio (UACR) of greater than 300 and less than 5000 or an eGFR of 25 to less than 50 ml/min/1.73m2 and a UACR greater than 100 and less than 5000.

The primary outcome of interest for the trial was major kidney disease events, which investigators defined as 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. Investigators also included a bevy of secondary outcomes of interest, which were tested hierarchically.

Upon analysis, 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). Further analysis 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) for kidney-specific components of the primary outcome. Additionally, analysis of death from cardiovascular causes pointed to a 29% reduction in risk relative to placebo therapy (HR, 0.71; 95% CI, 0.56 to 0.89).

Secondary outcomes analysis found secondary outcomes of interest, results demonstrated each of the confirmatory outcomes favored the semaglutide arm of the trial, including a slower decline of eGFR (difference, 1.16 ml/min/1.73m2; P <.001), reduced risk of major cardiovascular events (HR, 0.82; 95% CI, 0.68 to 0.98; P = .029), and all-cause mortality (HR, 0.80; 95% CI, 0.67 to 0.95; P = .01). In regard to the agent’s safety in the trial, results indicated adverse events were reported in a lower percentage of participants in the semaglutide group than among the placebo group (49.6% vs 53.8%).

With an interest in learning more about the landmark trial and its implications, HCPLive sat down with Perkovic following the presentation. That conversation is the subject of the video interview found above.

Disclosures of interest for Perkovic include AstraZeneca, Novo Nordisk, GlaxoSmithKline, 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