A collaborative research team has revealed new insights into how tirzepatide affects muscle composition in people with type 2 diabetes, addressing key concerns about muscle loss during pharmacological weight reduction.
The post-hoc analysis of Eli Lilly's SURPASS-3 trial, conducted by AMRA Medical in partnership with researchers from the University of Glasgow, University Hospitals Cleveland, and Eli Lilly and Company, examined the relationship between tirzepatide treatment and changes in muscle composition among patients with type 2 diabetes.
Key Findings on Muscle Composition
The analysis, which included data from over 200 participants, revealed that decreases in muscle volume with tirzepatide largely followed the expected pattern based on overall weight reduction. However, researchers observed that decreases in muscle fat infiltration were more pronounced than would be expected from weight loss alone.
"The results of this study are important as many people remain concerned about the muscle effects of newer weight loss drugs," said Professor Naveed Sattar, the study's first author. "However, these new data suggest that the amount of muscle volume changes with tirzepatide appears to be in line with muscle volume changes seen in the population for similar differences in weight. More importantly, these data suggest a clear reduction in the amount of fat in muscles, changes that may in fact improve muscle efficiency."
The findings suggest an adaptive response to weight reduction for muscle volume and a potentially positive effect on muscle fat infiltration following tirzepatide treatment in this population.
Advanced Imaging Techniques Provide New Insights
The research team utilized AMRA's MRI-based technology (AMRA® Researcher) to analyze changes in thigh muscle volume, muscle volume z-score, and muscle fat infiltration. This approach represents a significant advancement over previous studies that relied on DEXA scanning, which provides less detailed information about muscle mass and fat infiltration (myosteatosis).
This study builds upon previous collaborative work between AMRA and Lilly on the SURPASS-3 MRI substudy, which demonstrated that tirzepatide treatment was associated with favorable body fat redistribution, particularly with significant visceral and liver fat loss beyond what would be expected from weight reduction alone.
Clinical Significance for Anti-Obesity Medications
As anti-obesity medications continue to achieve greater weight reductions, understanding their impact on muscle composition becomes increasingly important. Excessive muscle loss could potentially lead to reduced muscle strength, mobility, and long-term physical performance—concerns that are particularly relevant for vulnerable patient populations.
The study provides reassurance that tirzepatide's effect on muscle volume appears proportionate to weight loss, while its ability to reduce fat within muscle tissue may actually improve muscle function.
Advancing Precision Medicine
The research represents an important milestone in developing reference data for weight-invariant assessment of fat and muscle biomarkers through AMRA's z-score biomarker technology. It also serves as the first report describing the associations between incretin-based therapies and changes in muscle composition in type 2 diabetes using gold-standard MRI technology.
As the metabolic drug development landscape evolves rapidly, these advanced biomarkers provide insights beyond simple weight loss metrics, allowing researchers and clinicians to better understand how emerging therapies affect body composition and function.
The full publication, titled "Tirzepatide and muscle composition changes in people with type 2 diabetes: A post-hoc analysis from a randomised, open-label, parallel-group, phase 3 trial (SURPASS-3 MRI)," appears in The Lancet Diabetes & Endocrinology.
