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The STEP trial program provides the most detailed fatigue data of any GLP-1: STEP-1: ~11% fatigue at 2.4mg STEP-3: 12.8% the highest rate, in the trial combining semaglutide with intensive behavioral therapy (suggesting that aggressive lifestyle changes compound drug-induced fatigue) STEP-8: 9.5% semaglutide vs 4.7% liraglutide vs 0% placebo direct evidence that semaglutide causes more fatigue than the older GLP-1 A pooled meta-analysis of 50 semaglutide trials found a relative risk of 4.23 for asthenia (95% CI 1.34-13.36) with zero heterogeneity (I=0%) meaning the ~4-fold excess risk was consistent across every trial, not driven by outliers

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