Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes

The FLOW (Evaluate Renal Function with Semaglutide Once Weekly) trial was a randomized, double-blind, placebo-controlled, event-driven study evaluating whether semaglutide could slow the progression of chronic kidney disease in patients with type 2 diabetes. A total of 3,533 participants with eGFR of 25 to 75 mL/min/1.73 m² and elevated albuminuria were randomized to weekly semaglutide 1.0 mg or placebo, with a median follow-up of 3.4 years. The trial was stopped early after a pre-specified efficacy analysis.

The composite primary endpoint included kidney failure (dialysis, transplantation, or persistent eGFR <15), >=50% reduction in eGFR from baseline, death from kidney causes, and death from cardiovascular causes. The results were robust:

• 24% reduction in the risk of the primary outcome (HR 0.76; 95% CI 0.66-0.88; P=0.0003)
• 21% reduction in the kidney-specific composite endpoint (HR 0.79)
• 29% reduction in cardiovascular death (HR 0.71)
• Attenuation of annual eGFR decline by 1.16 mL/min/1.73 m²/year (P<0.001)

Secondary analyses showed a 20% reduction in MACE (major adverse cardiovascular events) and 20% in all-cause mortality, with consistent benefits across subgroups of baseline eGFR, SGLT2 inhibitor use, and albuminuria severity. The safety profile was favorable, with no signals of acute kidney adverse events.

FLOW represents a landmark in nephrology, establishing semaglutide as the first GLP-1-based therapy with demonstrated renal and cardiovascular benefit in patients with diabetic kidney disease. These data led to an expanded indication for the drug and repositioned GLP-1 agonists as a therapeutic pillar — alongside SGLT2 inhibitors and renin-angiotensin system blockers — in the management of diabetic nephropathy.