College of Medical, Veterinary & Life Sciences

A recent analysis of the SURPASS-3 trial unravels the impact of treatment with the drug tirzepatide on muscle volume and fat infiltration in individuals with Type 2 Diabetes.

Published in The Lancet Diabetes & Endocrinology, the study is the result of a research collaboration lead by Professor Naveed Sattar from the University of Glasgow, alongside colleagues from University Hospitals Cleveland, AMRA Medical and Eli Lilly and Company. The research team explored data from the SURPASS-3 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.

The results suggested that treatment with tirzepatide was associated with a shift towards a more favourable 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 analysis, which included data from over 200 participants, 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 analysis provides 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 – 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, first author of the study, said: “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.”

The study, “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)”, is published in The Lancet Diabetes & Endocrinology.

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Enquiries: ali.howard@glasgow.ac.uk or elizabeth.mcmeekin@glasgow.ac.uk

First published: 30 April 2025