How does muscle composition change after weight loss from tirzepatide in patients with diabetes?

Patients on tirzepatide for 52 weeks saw significantly reduced muscle fat infiltration (myosteatosis) as well as reduced muscle volume, in the context of weight loss and metabolic improvements, in this SURPASS-3 MRI substudy. The reduced muscle volume seen with tirzepatide was consistent with the general association between body weight and muscle volume calculated from population-based estimates of non-pharmacologic weight changes. However, the reduced myosteatosis seen with tirzepatide was greater than the general association with body weight, suggesting a potentially positive effect on muscle fat infiltration.

• Study details: The multinational, multicenter SURPASS-3 trial randomized insulin-naive adults with type 2 diabetes on metformin to tirzepatide at 5/10/15 mg vs. titrated insulin degludec. In this post-hoc analysis (N=246; mean age, 56 years; type 2 DM duration, 6.7 years; mean HbA1c 8.3%; mean BMI 33.4; SGLT-2 inhibitor use, 31%), MRI muscle volume and thigh-muscle fat infiltration differences at baseline and week 52 were analyzed. Researchers then used paired t-tests to compare study data to population-based estimates calculated from longitudinal data in the UK Biobank (N=2942), factoring body weight.
• Results: Patients on tirzepatide (all doses) saw muscle volume decreases consistent with the associations between muscle volume and body weight estimated from UK Biobank data. However, the myosteatosis reductions seen with tirzepatide were significantly greater than population-based calculated estimates (p<0.0001).
• Clinical impact: Researchers concluded that the changes in muscle volume were suggestive of an adaptive response to weight reduction, and that there was a potentially positive effect on myosteatosis in study patients.

Source:

Sattar N, et al. (2025, April 30). Lancet Diabetes Endocrinol. 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. https://pubmed.ncbi.nlm.nih.gov/40318682/