medwireNews: People with type 2 diabetes who experience clinically meaningful weight loss during tirzepatide treatment have significant reductions in muscle volume and muscle volume Z score, but also favorable reductions in muscle fat infiltration, show data from the SURPASS-3 MRI substudy.
“When contextualised with longitudinal data from the UK Biobank, the results suggested that decreases in muscle volume with tirzepatide largely followed the general association between changes in muscle volume and bodyweight, whereas decreases in muscle fat infiltration appeared to be greater than the effect of the association with bodyweight,” write Naveed Sattar (University of Glasgow, UK) and co-authors in The Lancet Diabetes & Endocrinology.
The post-hoc analysis of the randomized SURPASS-3 study included data for 246 people with metformin-treated type 2 diabetes (mean age 56 years, 60% men) who had their thigh muscle composition measured by magnetic resonance imagining (MRI) before and after 52 weeks of subcutaneous treatment with tirzepatide (5, 10, or 15 mg once weekly) or daily titrated insulin degludec.
At baseline, the study participants had a median type 2 diabetes duration of 6.7 years, a mean glycated hemoglobin level of 8.3% (67 mmol/mol), and a mean BMI of 33.4 kg/m2. All were insulin-naïve but 30.9% were using a sodium-glucose cotransporter-2 inhibitor.
The researchers report that, during treatment, participants given tirzepatide had a significant pooled mean weight loss of 10.1% compared with a weight gain of 3.3% among those given insulin degludec.
The weight loss in the pooled tirzepatide group was accompanied by a significant mean 0.36 percentage point reduction in thigh muscle fat infiltration at week 52, from a baseline of 8.1%, as well as a significant mean 0.64 L reduction in thigh muscle volume from a baseline of 10.8 L.
In addition, thigh muscle volume Z score, which describes how much the muscle volume in each participant deviates from the average among sex- and BMI-matched individuals, fell by a significant 0.22 units, on average, during tirzepatide treatment, from a baseline of –0.48 units.
Changes in muscle fat infiltration, muscle volume, and muscle volume Z score from baseline were also significant across all individual doses of tirzepatide.
For participants given insulin degludec, muscle volume increased by a significant mean 0.16 L from baseline to week 52, but there was no significant change in muscle volume Z score or muscle fat infiltration, and the changes in all three muscle composition measures differed significantly between the pooled tirzepatide and insulin degludec groups.
To put the findings into context, Sattar et al compared the changes in muscle composition among the SURPASS-3 MRI substudy participants with those among 2942 UK Biobank participants with longitudinal MRI data.
They found that the reductions in muscle fat infiltration and muscle volume Z score were significantly greater in the pooled tirzepatide group than in the UK Biobank group, at a mean difference of 0.42 percentage points and 0.12 units, respectively.
By contrast, there was no difference between the two cohorts in the change in muscle volume, which indicates that “tirzepatide did not seem to be associated with accelerated muscle loss in this population (at least based on the metric of muscle volume),” the researchers remark.
Also, the differences in muscle fat infiltration reductions between the two cohorts were significant at all tirzepatide doses, they note, whereas the differences in muscle volume Z score were only significant at the 15 mg dose and this “was balanced by a significant additional reduction in muscle fat infiltration […] suggesting a potentially neutral effect on strength and physical performance.”
Sattar and co-authors conclude that their findings “support the clinical benefits observed in clinical trials with tirzepatide and provide additional evidence regarding the potential metabolic effects of this dual [glucose-dependent insulinotropic polypeptide] and [glucagon-like peptide]-1 receptor agonist.”
They continue: “Additional studies with more specific designs are needed to further investigate how these MRI data translate into long-term changes in muscle strength, mobility, and physical performance in people treated with tirzepatide.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of the Springer Nature Group
Lancet Diabet Endocrinol 2025; doi:10.1016/S2213-8587(25)00027-0
