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

Nephrol Dial Transplant. 2023 Jan 18;gfad009. doi: 10.1093/ndt/gfad009. Online ahead of print.


Background: Chronic kidney disease (CKD) is a common complication of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and lower body weight in people with T2D, and some reduce risk of cardiovascular (CV) events in those with high CV risk. GLP-1RAs might also have kidney-protective effects. We report the design and baseline data for FLOW, a trial investigating the effects of once-weekly (OW) GLP-1RA semaglutide on kidney outcomes in participants with CKD and T2D.

Methods: FLOW is a randomised, double-blind, parallel-group, multinational, phase 3b trial. Participants with T2D, estimated glomerular filtration rate (eGFR) ≥50‒≤75 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) >300‒<5,000 mg/g or eGFR ≥ 25‒<50 mL/min/1.73 m2 and UACR > 100‒<5,000 mg/g, were randomised 1:1 to OW semaglutide 1.0 mg or matched placebo, with renin-angiotensin-aldosterone system blockade (unless not tolerated/contraindicated). The composite primary endpoint is time to first: kidney failure (persistent eGFR <15 mL/min/1.73 m² or initiation of chronic kidney replacement therapy); persistent ≥ 50% reduction in eGFR; or death from kidney or CV causes.

Results: Enrolled participants (N = 3 534) had a baseline mean (SD) age of 66.6 (9.0) years, HbA1c of 7.8 (1.3) %, diabetes duration of 17.4 (9.3) years, eGFR of 47.0 (15.2) mL/min/1.73 m2 and median UACR of 568 (range: 2‒11 852) mg/g. According to Kidney Disease: Improving Global Outcomes guideline categorisation, 68.2% were at very high risk for CKD progression.

Conclusion: FLOW will evaluate the effect of semaglutide on kidney outcomes in participants with CKD and T2D, and is expected to complete in late 2024.

Keywords: albuminuria; cardiovascular disease; diabetic kidney disease; glomerular filtration rate; glucagon-like peptide-1 receptor agonist.