SURPASS-3 trial: Tirzepatide’s impact on muscle composition

A recent analysis of the SURPASS-3 trial indicates 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 is a research collaboration led by Professor Naveed Sattar from the University of Glasgow, alongside colleagues from University Hospitals Cleveland, AMRA Medical and Eli Lilly and Company. The 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 toward 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.

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.

"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,” explained Sattar, first author of the study. "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 were reported in the paper, ‘Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial’, The Lancet Diabetes & Endocrinology. To access this paper, please click here