Semaglutide reduced the risk of major kidney outcomes in patients with type 2 diabetes and chronic kidney disease regardless its severity: FLOW trial
Presenter: Katherine R. Tuttle, MD, Executive Director for Research, Providence Inland Northwest Health, Spokane, WA.
Semaglutide safely and effectively reduces the risks of major kidney outcomes regardless of chronic kidney disease (CKD) severity in patients with diabetes and CKD.
In patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) severity, semaglutide safely reduced risks of major kidney outcomes regardless of the CKD severity, according to this analysis of FLOW trial results presented during the Kidney Week 2024. It also reduced the risks of cardiovascular events and all-cause mortality, according to study author Katherine R. Tuttle, MD, Executive Director for Research, Providence Inland Northwest Health, Spokane, WA.
The multinational, randomized, controlled FLOW trial included 3,533 adults with T2D (HbA1c ≤10%) receiving a renin angiotensin system inhibitor and having an estimated glomerular filtration rate (eGFR) between 50 and 75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) between 300 and 5000 mg/g OR eGFR between 25 and 50 mL/min/1.73 m2 and UACR between 100 and 5,000 mg/g. All received once-weekly subcutaneous semaglutide (1.0 mg) plus standard of care or placebo plus standard of care. In primary FLOW study results, semaglutide reduced the risk of major kidney outcomes, cardiovascular events, and death from any cause by 24% (N Engl J Med. 2024;391:109-21 DOI: 10.1056/NEJMoa2403347).
This analysis looked at kidney outcomes according to baseline CKD severity as assessed by four levels of baseline levels of estimated glomerular filtration rate [eGFR]: <30, ≥30 to <45, ≥45 to <60, ≥60 mL/min/1.73 m2) and five levels of urinary albumin-to-creatinine ratio (UACR): <100, ≥100 to <300, ≥300 to <1000, ≥1000 to <2000, ≥2000 mg/g. The primary outcome was time to first occurrence of major kidney events consisting of onset of persistent reduction (≥50%) in eGFR compared with baseline, kidney failure (onset of persistent eGFR <15 mL/min/1.73 m2, initiation of chronic kidney replacement therapy [either dialysis or kidney transplantation]), kidney death, or cardiovascular death.
For the composite kidney events, Dr. Tuttle reported the following hazard ratios (HR) and 95% confidence intervals (CI) for semaglutide versus placebo based on baseline eGFRs (P = .833 for all groups):
- <30 mL/min/1.73 m2: HR 0.81 (95% CI 0.58-1.13)
- ≥30 to <45: HR 0.74 (95% CI 0.59-0.92)
- ≥45 to <60 mg/g: HR 0.78 (95% CI 0.58-1.04)
- ≥60 mg/g: HR 0.64 (95% CI 0.43-0.96)
- Full analysis set: HR 0.76 (95% CI 0.66-0.88).
For the composite kidney events based on UACR levels, results were as follows (P = .282 for all groups):
- <100 mg/g: HR 0.70 (95% CI 0.34-1.44)
- ≥100 to <300: HR 0.92 (95% CI 0.60-1.41)
- ≥300 to <1000: HR 0.81 (95% CI 0.62-1.05)
- ≥1000 to <2000: HR 0.67 (95% CI 0.50-0.90)
- ≥2000: HR 0.61 (95% CI 0.47-0.79)
- Full analysis set: HR 0.76 (95% CI 0.66-0.88).
Semaglutide safely reduced the risks of major kidney outcomes, Dr. Tuttle said, irrespective of CKD severity defined by baseline eGFR or UACR in participants with T2D and CKD in the FLOW trial. “Semaglutide,” she concluded, “saves kidneys.”
Funding
- Commercial Support – Novo Nordisk