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7 Multi-center, double-blind, randomized, placebo-controlled, event-driven superiority trail 804 participating clinical sites in 41 countries Enrollment Criteria Intervention o 1:1 double-blinded non-stratified randomization to receive either 2.4mg semaglutide SC weekly or placebo o Initial dose of 0.24mg weekly x 4 weeks, uptitrated to 0.5, 1.0, 1.7, and eventually 2.4mg every 4 weeks If significant adverse effects encountered, patients could be placed on slower uptitration, pause treatment, or continue reduced maintenance dose therapy o Placebo/semaglutide discontinued if: Patients became/planned to become pregnant Developed pancreatitis Calcitonin level 100 ng/L Patients were to continue on treatment if diabetes was diagnosed after initiation of treatment/placebo Primary Outcome Composite of death from cardiovascular causes, nonfatal MI, nonfatal stroke, (assessed in time-to-first-event analysis) Secondary Outcome: (all assessed in time-to-first-event analysis) Death from cardiovascular causes Composite heart failure end-point (death from CV causes or hospitalization/urgent medical visit for heart failure) Death from any cause Statistical Analysis o Event-driven trial designed to provide 90% power to detect relative risk reduction of 17% for primary endpoint (HR 0.83) at overall one-sided significance level of 0.025 o Required minimum 1225 primary end-point events accrued o Intention-to-treat analysis performed o Hazard ratios and 95% confidence intervals generated with Cox proportional hazard model Baseline Characteristics 17604 patients randomized between Oct

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