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Latest Data from SURPASS-3 Trial Gleans Insight Into the Association of Tirzepatide Treatment with Changes in Muscle Composition in Type 2 Diabetes

1.5.2025 13:00:00 CEST | Business Wire | Press release

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A recent post-hoc analysis of Lilly’s SURPASS-3 trial unravels the impact of tirzepatide treatment on muscle volume and fat infiltration in individuals with Type 2 Diabetes

AMRA Medical, as part of a collaborative effort composed of researchers from the University of Glasgow, University Hospitals Cleveland, and Eli Lilly and Company, recently conducted a detailed post-hoc analysis of Lilly’s SURPASS-3 trial. The analysis explored data from the trial to determine the association of tirzepatide treatment with changes in thigh muscle volume, muscle volume z-score and muscle fat infiltration in people with type 2 diabetes (T2D)

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A recent post-hoc analysis of Lilly’s SURPASS-3 trial unravels the impact of tirzepatide treatment on muscle volume and fat infiltration in individuals with Type 2 Diabetes

The recent publication builds on previous joint efforts between AMRA and Lilly regarding the SURPASS-3 MRI substudy, which used AMRA’s unique, MRI-based visceral, subcutaneous, and liver fat z-score biomarkers to investigate changes in fat distribution patterns. The results suggested that treatment with tirzepatide was associated with a shift towards a more favorable body fat distribution with prominent visceral and liver fat loss, indicating a potential targeted effect beyond that expected by the magnitude of weight reduction.

Findings from this latest post-hoc analysis, which included data from over 200 participants analyzed using AMRA® Researcher, indicate that decreases in muscle volume with tirzepatide largely followed the overall association between changes in muscle volume and body weight, while decreases in muscle fat infiltration appeared to be larger. These data 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.

The study provides the field with highly anticipated data on muscle-related changes with pharmacologically induced weight reduction. In general, past studies have been limited by reporting gross changes in body composition using DEXA, which did not provide information on either muscle mass or myosteatosis. As anti-obesity medications are achieving greater weight reductions, it is important to determine if treatments under development are associated with an excess decrease in muscle mass (i.e., indicating a maladaptive response to weight loss), potentially leading to reduced muscle strength, mobility, and long-term physical performance – especially in more vulnerable patient populations.

Professor Naveed Sattar, the first author remarked that “The results of this study are important as many people remain concerned about the muscle effects of newer weight loss drugs. 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.”

Additionally, the study marks another important milestone in AMRA’s pursuit to provide the field with reference data for weight-invariant assessment of fat and muscle biomarkers through the unique z-score biomarker technology from trials such as SURPASS-3 MRI. It also serves as the first report describing the associations between incretin-based therapies and changes in muscle composition in T2D using reliable, gold-standard MRI - perpetuating AMRA’s commitment to pioneering innovation in treatment differentiation in T2D and beyond. As the metabolic drug development landscape continues to unfold at dramatic pace, AMRA is at the forefront of designing effective biomarkers that elucidate insights beyond weight loss, allowing emerging therapies to demonstrate their safety and efficacy across a number of disease areas.

You can read the full publication in The Lancet Diabetes & Endocrinology, 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)”, here. You can also learn more about AMRA’s z-scores and how they’re changing how we think about weight-loss by viewing our latest insights article here.

About AMRA Medical

AMRA Medical is a health informatics and precision medicine company that is pioneering body composition analysis, providing cutting-edge solutions to advance both clinical research and patient care initiatives. AMRA's gold-standard technology delivers multiple fat and muscle biomarkers - derived simply from rapid whole-body MRI scans. AMRA is committed to driving transformative care and simplifying vital decision-making in both research and clinical care settings by offering support services via their innovative platform.

Learn more about AMRA Medical’s MRI-based solutions at https://amramedical.com/solutions, or connect with our team of experts for a detailed discussion at info@amramedical.com.

Follow AMRA on LinkedIn for the latest updates in fat distribution and muscle composition assessments in metabolic disease research and beyond.

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