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Across four JARDIANCE outcome trials, lower limb amputation event rates were 4.3 and 5.0 events per 1,000 patient-years in the placebo group and the JARDIANCE 10 mg or 25 mg dose group, respectively, with a HR of 1.05 (95 % CI) (0.81, 1.36)

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Hypoxia then stabilizes HIF-1 and upregulates REST, which suppresses GCLM/GPX4 expression and enhances ACSL4-dependent lipid peroxidationdirectly amplifying ferroptosiswhile also promoting the release of hypoxic extracellular vesicles (EVs) that propagate tubular ferroptosis in a paracrine manner