The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease.
FLOW is a phase 3b randomized trial testing whether once-weekly semaglutide 1.0 mg improves major kidney outcomes in 3,534 people with type 2 diabetes and chronic kidney disease; the trial subsequently demonstrated a significant reduction in the primary composite kidney endpoint.
Background
Chronic kidney disease is a common complication of type 2 diabetes. GLP-1 receptor agonists improve glycemic control and lower body weight, and some reduce cardiovascular events, with prior data suggesting potential kidney-protective effects such as reduced albuminuria and slower eGFR decline. FLOW was designed as a dedicated kidney outcomes trial of the once-weekly GLP-1 receptor agonist semaglutide.
Study design
FLOW (NCT03819153) was a randomized, double-blind, parallel-group, multinational phase 3b trial. Participants with type 2 diabetes and chronic kidney disease (eGFR 50 to 75 ml/min/1.73 m2 with urine albumin-to-creatinine ratio above 300 to below 5000 mg/g, or eGFR 25 to below 50 ml/min/1.73 m2 with ratio above 100 to below 5000 mg/g) were randomized 1:1 to once-weekly semaglutide 1.0 mg or placebo on a background of renin-angiotensin-aldosterone system blockade. The composite primary endpoint was time to first kidney failure, persistent 50% or greater eGFR reduction, or death from kidney or cardiovascular causes.
Key findings
The 3,534 enrolled participants had a mean age of 66.6 years, mean HbA1c of 7.8%, mean diabetes duration of 17.4 years, mean eGFR of 47.0 ml/min/1.73 m2, and a median urine albumin-to-creatinine ratio of 568 mg/g, with 68.2% classified at very high risk for CKD progression by KDIGO categories. In the subsequent primary results, semaglutide reduced the risk of the primary composite kidney outcome by 24% (hazard ratio 0.76; 95% CI 0.66 to 0.88), with consistent benefits across CKD severity strata and reductions in cardiovascular death and all-cause death.
Clinical implications
FLOW evaluates a kidney-specific outcome for a GLP-1 receptor agonist in a high-risk population with type 2 diabetes and chronic kidney disease, a group with substantial residual risk despite standard therapy. The demonstrated reduction in major kidney disease events positions once-weekly semaglutide as an additional renoprotective option alongside RAAS blockade and SGLT2 inhibition in this population.
Category
Research
Source
Nephrol Dial Transplant
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