Kidney, heart benefits FLOW with semaglutide

Semaglutide reduces the risk of major kidney disease-related events and death from cardiovascular causes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), as shown in the FLOW* study presented at ERA 2024.  

“These findings offer great promise in reshaping treatment strategies for individuals at high risk of diabetes-related complications, offering a new avenue for kidney and cardiovascular protection,” said study author Dr Vlado Perkovic, Dean of Medicine and Health and Scientia Professor at UNSW Sydney, Australia, who presented the results.

The trial, comprising 3,533 patients with T2D and CKD, was the first to investigate whether a glucagon-like peptide-1 (GLP-1) receptor agonist could prevent major kidney outcomes.

The patients (mean age 66 years, 30 percent female) were recruited from 28 countries between June 2019 and May 2021. They were randomly assigned to receive semaglutide 1.0 mg once weekly (n=1,767) or placebo (n=1,766), both in addition to standard care. [N Engl J Med 2024;doi: 10.1056/NEJMoa2403347]

Ninety-three percent had stage 3 or 4 CKD based on the KDIGO** criteria. About 95 percent were on a RAAS*** blocker, 60 percent were receiving an ARB+, 35 percent were on ACE⁺⁺ inhibitors, 80 percent were taking lipid-lowering drugs, and 15 percent were on an SGLT2⁺⁺⁺ inhibitor.

The trial was stopped early last year due to semaglutide efficacy, following a recommendation from an independent monitoring committee.

Reduction in major kidney events

At a median follow-up of 3.4 years,  patients treated with semaglutide vs placebo had a 24-percent reduction in major kidney events, defined as a composite of kidney failure onset (dialysis, transplantation, or an eGFR^# <15 mL/min/per 1.73 m²), at least a 50-percent reduction in eGFR from baseline, or death from kidney-related or CV causes (18.7 percent [331 events] vs 23.2 percent  [410 events]; hazard ratio [HR], 0.76; p=0.0003). The results were similar for the individual components of the primary outcome.

Additionally, the mean annual slope of eGFR was less steep with semaglutide than placebo, suggesting a slower decline in kidney function (p<0.001).

The semaglutide group had an 18-percent lower risk of MACE^# (HR, 0.82; p=0.029) and 20-percent lower risk of death from any cause (HR, 0.80; p=0.01). The incidence of serious adverse events was also lower with semaglutide relative to placebo (49.6 percent vs 53.8 percent).

Semaglutide is US-FDA approved to reduce the risk of cardiovascular events in adults with cardiovascular disease and either obesity or overweight, but is not currently licensed for diabetic kidney disease.

ERA president Dr Christoph Wanner, head of the Division of Nephrology at the University of Würzburg, Germany, said the results were remarkable, given the high rate of patients receiving cardiovascular treatment in the trial. “This gives us the reassurance that we can use this treatment.”