Trial
SELECT
Research Observatory
Evidence Update
Current evidence
SELECT compared semaglutide 2.4 mg weekly with placebo plus usual care in 17,604 adults aged at least 45 with established cardiovascular disease and BMI at least 27, without diabetes; the primary endpoint was major cardiovascular events. SELECT demonstrated fewer major cardiovascular events with semaglutide in adults with established cardiovascular disease and overweight/obesity without diabetes, alongside greater treatment discontinuation. SELECT's weight and kidney publications add endpoint-specific context from the same trial rather than new independent efficacy replications.
What changed
SELECT contributes one experiment; weight estimands differ and kidney-composite testing is nominal rather than multiplicity-confirmed.
What did not change
A secondary composite including macroalbuminuria is not proof of preventing kidney failure in all populations.
Why it matters
Makes clinical benefit usable without replication inflation or generalization.
Main limitation
Not general primary prevention, all body weights, longevity or an across-drug class effect. Kidney tests not multiplicity-adjusted; composite includes macroalbuminuria, not only kidney failure. No independent experiment added.
Next proof
Independent confirmation of kidney outcomes with multiplicity control, and clear treatment-policy versus on-treatment estimands.
Summary
SELECT compared semaglutide 2.4 mg weekly with placebo plus usual care in 17,604 adults aged at least 45 with established cardiovascular disease and BMI at least 27, without diabetes; the primary endpoint was major cardiovascular events. SELECT demonstrated fewer major cardiovascular events with semaglutide in adults with established cardiovascular disease and overweight/obesity without diabetes, alongside greater treatment discontinuation. SELECT's weight and kidney publications add endpoint-specific context from the same trial rather than new independent efficacy replications.
Intelligence Take
Makes clinical benefit usable without replication inflation or generalization.
Limitations
Not general primary prevention, all body weights, longevity or an across-drug class effect. Kidney tests not multiplicity-adjusted; composite includes macroalbuminuria, not only kidney failure. No independent experiment added.