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The trial program has evolved from glycemic-safety and outcomes studies in T2D (the LEADER, SUSTAIN-6, REWIND, EXSCEL, and PIONEER 6 era [10][13], [19]), to outcomes trials in expanded populations including obesity without diabetes (SELECT [3]), HFpEF with obesity (SUMMIT [5], with a companion semaglutide program in STEP-HFpEF [20], [21]), CKD (FLOW [22]), and an active-comparator setting (SURPASS-CVOT [6])

However, C4 was more strongly associated with breast cancer among individuals with a luminal B-like (HER2-positive or negative) subtype than other surrogate subtypes

L., Trammell, S

Option two: split the increase