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Tirzepatide associated with a potential targeted effect on visceral fat and liver fat

Exploratory analysis from the SURPASS-3 MRI study has shown a significant reduction of both visceral- and liver fat z-scores, and a shift towards a more balanced fat distribution pattern with tirzepatide treatment.

AMRA Medical's Personalized Fat Z-scores

Researchers from AMRA Medical, together with Eli Lilly, and researchers from Nantes Université, University Hospitals Cleveland, and Linköping University used visceral-, subcutaneous-, and liver fat z-scores derived from MRI 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 sub-study by comparison with sex- and BMI-matched virtual control groups (VCGs) derived from the UK Biobank imaging study at baseline and Week 52.

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.

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).

Absolute (or percent) change in body weight and/or BMI are still typical endpoints in clinical trials evaluating treatments for obesity and related disorders. However, the research team’s findings study suggest that pharmacological treatments for T2D may alter the fat distribution pattern in various ways - independent of changes in body weight. For this reason, fat distribution profiling through personalized z-score assessment would represent an attractive and modifiable endpoint for future therapeutic efficacy trials in obesity and related disorders.

“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,” the researchers concluded.

The personalized fat z-scores were introduced through research published in 2023 linking fat distribution patterns, as described by the z-scores, to specific cardiometabolic disease risk profiles in the general population. This was quickly followed by Surgery for Obesity and Related Diseases (SOARD) publishing results on risk-stratification of obesity class I & II by the fat z-scores in the American Society for Metabolic and Bariatric Surgery (ASMBS) guidelines/statements journal section of SOARD.

During follow-up of interventions that induce weight reduction, it has been difficult to determine whether a concurrent reduction of, e.g., visceral fat was in line with the amount of weight lost, or if there was larger reduction than expected. The significant reduction of visceral fat and liver fat z-scores observed with tirzepatide in SURPASS-3 MRI indicates a potential targeted effect beyond that expected by the magnitude of weight reduction.

The outcomes were featured in the paper, ‘Effect of tirzepatide on body fat distribution pattern in people with type 2 diabetes’, published in the journal Diabetes, Obesity and Metabolism. To access this paper, please click here


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