Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial
A prespecified analysis of the SELECT trial showed that once-weekly subcutaneous semaglutide 2.4 mg improved kidney outcomes in people with overweight or obesity and established cardiovascular disease without diabetes, reducing a composite kidney endpoint and slowing eGFR decline.
Background
Obesity is an important risk factor for declining kidney function and albuminuria. SELECT had previously demonstrated a 20% reduction in major adverse cardiovascular events with semaglutide versus placebo in patients with overweight/obesity and established cardiovascular disease but without diabetes. Whether this benefit extended to kidney outcomes in a non-diabetic population was examined in these prespecified analyses.
Study design
The SELECT trial randomized 17,604 patients (8,803 to semaglutide and 8,801 to placebo) to once-weekly subcutaneous semaglutide 2.4 mg or placebo, with a median follow-up of 182 weeks. The main composite kidney endpoint comprised death from kidney disease, initiation of chronic kidney replacement therapy, persistent eGFR below 15 mL/min/1.73 m2, persistent 50% or greater reduction in eGFR, or onset of persistent macroalbuminuria.
Key findings
The composite kidney endpoint occurred in 1.8% of the semaglutide group versus 2.2% of the placebo group (hazard ratio 0.78; 95% CI 0.63-0.96; P = 0.02), driven mainly by reduced onset of macroalbuminuria. The treatment benefit on eGFR at 104 weeks was 0.75 mL/min/1.73 m2 overall and 2.19 mL/min/1.73 m2 in patients with baseline eGFR below 60. Semaglutide was not associated with any excess of acute kidney injury.
Clinical implications
These results suggest semaglutide confers kidney benefit in individuals with overweight or obesity and cardiovascular disease even in the absence of diabetes, with the largest eGFR benefit in those with reduced baseline kidney function. The findings extend the cardio-kidney-metabolic role of semaglutide beyond diabetic populations.
Category
Research
Source
Nature Medicine
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