Effects of semaglutide with and without concomitant SGLT2 inhibitor use in type 2 diabetes and chronic kidney disease (FLOW trial)
In a prespecified FLOW trial analysis, semaglutide reduced kidney and cardiovascular outcomes in people with type 2 diabetes and chronic kidney disease, with no statistically significant interaction by baseline SGLT2 inhibitor use, suggesting benefits regardless of concomitant SGLT2 inhibitor therapy.
Background
People with type 2 diabetes and chronic kidney disease face high risks of kidney failure and cardiovascular complications. GLP-1 receptor agonists and SGLT2 inhibitors independently reduce cardiovascular and kidney events, but the effect of combining both classes was unclear.
Study design
FLOW participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2 inhibitor use (N=550) or no use (N=2,983) and randomized to semaglutide or placebo. The primary outcome was a composite of kidney failure, a 50% or greater reduction in eGFR, kidney death, or cardiovascular death.
Key findings
The primary outcome risk was 24% lower with semaglutide versus placebo across all participants (95% CI 12% to 34%). In the SGLT2 inhibitor subgroup the hazard ratio was 1.07 (95% CI 0.69-1.67; P=0.755) and in the non-SGLT2 inhibitor subgroup it was 0.73 (95% CI 0.63-0.85; P<0.001), with a P for interaction of 0.109. Treatment effects favoring semaglutide on total eGFR slope, major cardiovascular events, and all-cause death were similar regardless of baseline SGLT2 inhibitor use.
Clinical implications
The absence of a statistically significant interaction indicates that semaglutide's kidney and cardiovascular benefits appear consistent whether or not patients are already taking an SGLT2 inhibitor, supporting consideration of combined cardiorenal-protective therapy. The SGLT2 inhibitor subgroup was small, so its individual point estimate should be interpreted with caution.
Category
Research
Source
Nature Medicine
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