Effect of tirzepatide on body fat distribution pattern in people with type 2 diabetes

Abstract Aims To describe the overall fat distribution patterns independent of body mass index (BMI) in participants with type 2 diabetes (T2D) in the SURPASS‐3 MRI substudy by comparison with sex‐ and BMI‐matched virtual control groups (VCGs) derived from the UK Biobank imaging study at baseline and Week 52. Methods For each study participant at baseline and Week 52 ( N = 296), a VCG of ≥150 participants with the same sex and similar BMI was identified from the UK Biobank imaging study ( N = 40 172). Average visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT) and liver fat (LF) levels and the observed standard deviations (SDs; standardized normal z ‐scores: z ‐VAT, z ‐aSAT and z ‐LF) were calculated based on the matched VCGs. Differences in z ‐scores between baseline and Week 52 were calculated to describe potential shifts in fat distribution pattern independent of weight change. Results Baseline fat distribution patterns were similar across pooled tirzepatide (5, 10 and 15 mg) and insulin degludec (IDeg) arms. Compared with matched VCGs, SURPASS‐3 participants had higher baseline VAT (mean [SD] z ‐VAT +0.42 [1.23]; p < 0.001) and LF ( z ‐LF +1.24 [0.92]; p < 0.001) but similar aSAT ( z ‐aSAT −0.13 [1.11]; p = 0.083). Tirzepatide‐treated participants had significant decreases in z ‐VAT (−0.18 [0.58]; p < 0.001) and z ‐LF (−0.54 [0.84]; p < 0.001) but increased z ‐aSAT (+0.11 [0.50]; p = 0.012). Participants treated with IDeg had a significant change in z ‐LF only (−0.46 [0.90]; p = 0.001), while no significant changes were observed for z ‐VAT (+0.13 [0.52]; p = 0.096) and z ‐aSAT (+0.09 [0.61]; p = 0.303). Conclusion In this exploratory analysis, treatment with tirzepatide in people with T2D resulted in a significant reduction of z ‐VAT and z ‐LF, while z ‐aSAT was increased from an initially negative value, suggesting a possible treatment‐related shift towards a more balanced fat distribution pattern with prominent VAT and LF loss.