A 52-week study evaluated the effects of tirzepatide on muscle composition in adult patients with type 2 diabetes, focusing on changes in muscle fat infiltration and muscle volume.
Among 246 insulin-naive participants on metformin (with or without a sodium-glucose cotransporter 2 inhibitor), 190 received tirzepatide and 56 received insulin degludec. Baseline characteristics such as age, body mass index, and HbA1c were similar between the groups.
Participants treated with tirzepatide showed a mean reduction in muscle fat infiltration of 0.36 percentage points, a muscle volume decrease of 0.64 L, and a drop in muscle volume Z score of 0.22. These changes occurred alongside an average weight loss of 10.1%.
In contrast, participants receiving insulin degludec gained an average of 3.3% in body weight. Muscle volume increased slightly by 0.16 L, with no significant changes in muscle fat infiltration or muscle volume Z score.
Magnetic resonance imaging (MRI) assessments at baseline and week 52 showed that the reduction in muscle fat infiltration with tirzepatide exceeded expectations based on population data. In comparison, changes in muscle volume aligned with predictions for the amount of weight lost.
Subgroup analysis found no statistically significant differences in muscle composition changes by sex or baseline muscle metrics. However, older participants (≥ 60 years) had greater reductions in both body weight and muscle volume Z score compared with younger participants.
Weight loss was significantly correlated with reductions in muscle volume, fat infiltration, and muscle volume Z score. Muscle fat infiltration changes also correlated with lipid markers such as triglycerides, high-density lipoprotein cholesterol, and adiponectin.
The participants didn't receive standardized diet or exercise instructions. Muscle function wasn't directly assessed, although MRI-based muscle measures have been linked to functional outcomes in previous research.
The study was conducted at multiple international sites and funded by Eli Lilly and Company. Full disclosures are available in the original publication.