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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])
The difference in quality is significant
Urinary F2-isoprostane is the gold standard marker of lipid peroxidation, reliable for assessing oxidative stress
Because depleted glutathione impairs mitochondrial function and burdens the liver, the therapy is frequently paired with care for stubborn weight gain that has not responded to diet and exercise alone, supporting detoxification and metabolic efficiency rather than acting as a weight loss drug
