Hormonal
Tirzepatide is associated with significantly greater lean body mass (LBM) loss compared to semaglutide during routine care, with excess relative LBM losses of 1.1% to 2.0% at 3, 6, 9, and 12 months respectively.
If you are taking tirzepatide, expect to lose more lean muscle mass than if you were taking semaglutide for the same amount of weight loss. This effect increases with higher doses and longer duration. To counteract this, prioritize resistance training and adequate protein intake, and monitor your body composition, not just scale weight.
Tirzepatide was associated with greater relative lean body mass (LBM) loss than semaglutide at each measured time point, with excess LBM losses of 1.1%, 1.5%, 1.3% and 2% at 3, 6, 9 and 12 months, respectively.
Why this rating
Large observational cohort (n=7,965 with paired data) with statistical significance, but observational design limits causal inference.
Source
Greater lean-body-mass decline with tirzepatide than semaglutide in routine care, revealed by body-composition digital phenotyping
Karthik Murugadoss et al. · medRxiv · 2026
DOI 10.64898/2026.04.11.26350687
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