A new analysis of the SURPASS-3 trial sheds light on how tirzepatide, a medication for type 2 diabetes, influences muscle composition—specifically muscle volume and fat infiltration.
Led by Professor Naveed Sattar of the University of Glasgow, the research was conducted in collaboration with experts from University Hospitals Cleveland. The team investigated how tirzepatide treatment impacts thigh muscle volume, muscle volume z-scores, and muscle fat infiltration in individuals with type 2 diabetes.
Published in The Lancet Diabetes & Endocrinology, the findings suggest tirzepatide promotes a healthier body fat distribution, with notable reductions in visceral and liver fat. This indicates the drug may exert targeted metabolic benefits beyond what would be expected from weight loss alone.
The study, which analyzed data from over 200 participants, found that decreases in muscle volume largely paralleled weight loss. However, the reduction in muscle fat infiltration was even greater, pointing to a potentially beneficial adaptation in muscle quality during tirzepatide-induced weight loss.
These results provide much-needed insights into how pharmacological weight loss affects muscle health. Previous studies often relied on DEXA scans, which offer limited detail on muscle mass and fat infiltration (myosteatosis). As weight-loss medications become more potent, evaluating their impact on muscle composition is critical—especially to ensure they don’t lead to harmful reductions in muscle mass that could impair strength and mobility.
Commenting on the findings, Professor Sattar said:
“These results are significant because many people worry about muscle loss with newer weight-loss medications. However, our data suggest that muscle volume changes with tirzepatide align with what’s typically seen for comparable weight loss. Importantly, we observed a clear decline in muscle fat content, which could actually enhance muscle efficiency.”
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