https://doi.org/10.55788/66f35841
The phase 3, global, randomised, controlled FLOW trial (NCT03819153) randomised 3533 participants 1:1 to semaglutide 1mg weekly or placebo, with all participants receiving background standard-of-care therapy. The trial design, primary, cardiovascular, and safety outcomes were presented by multiple speakers at the ERA 2024 [1–4].
The FLOW trial included adults with type 2 diabetes (HbA1c ≤10%), who had additional chronic kidney disease (eGFR of 50–75 mL/min/1.73 m2, urinary albumin-to-creatinine ratio between >300 and <5000 mg/g, or eGFR of 25 to <50 mL/min/1.73 m2, urinary albumin-to-creatinine ratio between >100 and <5000 mg/g). The primary endpoint was the time-to-first occurrence of persistent ≥50% eGFR reduction from baseline, kidney failure (persistent eGFR <15 mL/min/1.73 m2, dialysis or kidney transplant), kidney-related mortality or cardiovascular death.
The trial was stopped early as it reached the pre-specified boundaries of superiority of the new treatment: After a median of 3.4 years, 18.7% of participants receiving semaglutide reached the primary endpoint compared with 23.2% of participants receiving placebo (HR 0.76; 95% CI 0.66–0.88; P=0.0003). 12.3% of participants with semaglutide versus 14.7% of control participants achieved the composite outcome excluding cardiovascular death (HR 0.79; 95% CI 0.66–0.94), while the mean loss of kidney function rate was -2.19 mL/min/1.73 m2/year compared with -3.36 mL/min/1.73 m2/year (1.16 mL/min/1.73 m2/year difference; P<0.001) [1]. Semaglutide also showed significantly lower rates of major adverse cardiac events (12.0% vs 14.4%; HR 0.82; 95% CI 0.68–0.98; P=0.029) compared to placebo [3]. Overall, serious adverse events were more common in the placebo group (53.8% vs 59.6%), with infections, infestations, and cardiac adverse events as the most common adverse events in both groups [4].
“The FLOW trial demonstrated a 24% lower risk of the primary outcome with the consistency of the kidney components of the primary outcome”, concluded Prof. Vlado Perkovic (University of New South Wales, Sydney, Australia), the lead investigator of the trial [2]. These results are particularly promising in combination with the similar safety outcomes in the two groups.
- Pratley R, et al. FLOW trial design and baseline characteristics. Plenary Session, ERA 2024, 23–26 May, Stockholm, Sweden.
- Perkovic V, et al. FLOW primary efficacy results. Plenary Session, ERA 2024, 23–26 May, Stockholm, Sweden.
- Mahaffey KW, et al. FLOW CV outcomes. Plenary Session, ERA 2024, 23–26 May, Stockholm, Sweden.
- Mann JFE, et al. FLOW safety outcomes. Plenary Session, ERA 2024, 23–26 May, Stockholm, Sweden.
Medical writing support was provided by Mihai Surducan, PhD.
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Table of Contents: ERA 2024
Featured articles
Meet the Experts: Navigating Kidneys and Genes
Chronic Kidney Disease
FLOW-trial: Semaglutide improves kidney and cardiovascular outcomes in type 2 diabetes and chronic kidney disease
Early phase data show albuminuria improvement with avenciguat
Rilparencel leads to kidney function stabilisation in chronic kidney disease and type 2 diabetes
The majority of real-world patients with CKD are not eligible for SGLT2 inhibitor trials
Kidney Transplantation and Dialysis
CD38 inhibition by felzartamab promising for resolution of antibody-mediated rejection following kidney allografts
TATH trial: Twice-weekly haemodialysis can be an alternative to thrice weekly regimen
KIR-HLA class I mismatch could be involved in antibody-mediated rejection of transplanted kidneys
IgA Nephropathy
Atrasentan shows positive interim results in IgA nephropathy: ALIGN phase 3 trial
Zigakibart slows down eGFR decline in IgA nephropathy
Long-term atacicept shows continued benefit in IgA nephropathy
APPLAUSE-IgAN: Iptacopan improves proteinuria in IgA nephropathy
Cardio-Renal Interplay
Semaglutide improves renal outcomes in overweight/obese participants with cardiovascular disease and no diabetes
Discrepancy between cardiovascular RCT participants and real-life CKD patients could limit generalisability of RCT results
MERCURI-1: Perioperative empagliflozin shows renal protection following cardiac surgery
Simulated head-to-head comparison of SGLT-2 inhibitors and GLP-1R agonists in type 2 diabetes
Other Nephrology
Preview of the new KDIGO Guidelines for ADPKD, available later in 2024
APPEAR-C3G: Iptacopan shows promise for complement 3 glomerulopathy
Anti-nephrin autoantibody positivity describes a unique subclass of podocytopathies
Active vitamin D plus low-dose prednisolone is an alternative to high-dose prednisolone in minimal change disease
Claudin-1 is a potential antibody target for crescent glomerulonephritis
Rituximab protocol based on PLA2R1 epitope spreading outperforms the standard GEMRITUX protocol in membranous nephropathy
The REACT score predicts relapse in ANCA-associated vasculitis
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