Tirzepatide significantly reduced visceral and liver fat by more than weight loss in 2022 EASD

Translator: Tang Keke, Department of Endocrinology, Affiliated Hospital of Ningbo University School of Medicine

Introduction: From September 19 to 23, 2022, the 2022 European Association for the Study of Diabetes Annual Conference, a major international conference in the field of endocrinology, was held
in Stockholm, Sweden in the form of "online + offline".
At the meeting, scholars shared a study
entitled "Tirzepatide shows beneficial effects on body fat distribution patterns in patients with type 2 diabetes".

To explore the effect of Tirzepatide on the distribution pattern of body fat in type 2 diabetes mellitus compared to insulin degludec

With the advancement of diabetes treatment drugs, a novel dual GIP and GLP-1 receptor agonist Tirzepatide (TZP)
has emerged.
In the MRI subgroup study of SURPASS-3, patients with type 2 diabetes mellitus (metformin tablets and/or SGLT-2i treatment, HbA1c7-10.
5%, BMI ≥25 kg/m2, fatty liver index ≥60) were randomized into 4 groups: TZP5 mg once a week (N=71) and TZP10mg once a week (N=79), TZP 15 mg once a week (N=72) and insulin degludec once a day (N=74).

The results showed that the patients in the TZP treatment group achieved an average weight loss of 9.
6 kg, and the MRI assessment of visceral fat (VAT), abdominal subcutaneous fat (aSAT) and liver fat (LF) were significantly reduced.
However, the patients in the insulin Deglu treatment group increased their body weight by an average of 3.
2kg, visceral fat and subcutaneous fat on the abdomen, and the decrease in liver fat was significantly lower than that in the TZP treatment group
.
This study aims to describe the overall fat distribution pattern at baseline and week 52 and to correlate
actual changes in fat banks with changes in differential predictions from two dummy control groups (VCGs) matched baseline and 52 week data.

Results: Tirzepatide significantly reduced visceral and liver fat

The UK Biobank imaging study system (N=40174) was used to collect information for each patient who participated in the baseline examination and 52 weeks follow-up, and confirmed the sex and similar body size (height, weight, BMI)
of more than 150 participants.
The calculation of expected levels of VAT, aSAT, and LF and deviations from expected levels is based on individualized VCG matching (standardized normal z-scores (VATz, aSATz, LFz)); = standard deviation [SD]).

z-score changes from baseline examination to week 52 were calculated to describe changes in fat distribution patterns, magnitudes of changes in VAT, aSAT, and LF, and compared to
observed weight changes.

The results showed that the baseline fat distribution pattern was similar
between the TZP aggregate group and the IDeg group.
Study participants had higher baseline VAT [mean (SD) VATz=0.
42 (1.
23), p<0.
001] and LF [LFz=1.
24(0.
92), p<0.
001] compared to matched VCGs, but similar aSATs (aSATz=-0.
13(1.
11), p=0.
083).

VATz [-0.
18 (0.
58), p<0.
001] and LFz [-0.
54 (0.
84), p<0.
001] were significantly reduced in patients treated with TZP, while aSATz increased [0.
11 (0.
50), p=0.
011], indicating a significant reduction in VAT and LF, while the reduction in aSAT was much less
than predicted by the observed weight loss.

Compared with the predicted weight loss observed after VCG matching, patients in the TZP group had an average reduction of 0.
31 L (p<0.
001), an average reduction of 5.
64% (p<0.
001) more LF, and an average reduction of 0.
16 L (p=0.
018)
in aSAT.

Fig.
1 Changes in fat distribution pattern after treatment in TZP group and IDeg group

Note: Clinical trial registration number: NCT03882970 sub-study (sponsored by Eli Lilly & Company)

conclusion

The study showed that T2D patients and those with skewed fat distribution patterns had higher VAT and LF compared to matched VCGs, and that TZP treatment resulted in a greater reduction in VAT and LH than predicted by the observed weight loss alone, indicating a targeted and potentially beneficial shift
in fat distribution patterns.

Translator's introduction

Deputy Chief Physician, Department of Endocrinology, Affiliated Hospital of Ningbo University School of Medicine

Graduated from Zhejiang University with a master's degree, he has been engaged in endocrinology for more than 10 years, and has studied in Shanghai Ruijin Hospital for half a year

At present, he is a youth committee member of the Endocrinology Branch of Ningbo Medical Association, and the teaching secretary of the Internal Medicine Base of the Affiliated Hospital of Ningbo University School of Medicine

He has presided over and participated in a number of provincial and municipal projects, published nearly 10 articles, and won awards
in many provincial and municipal competitions.