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. 2024 Oct;16(10):503-508.
doi: 10.14740/jocmr6031. Epub 2024 Oct 30.

Elevated Serum Growth Differentiation Factor 15 Levels as a Potential Biomarker of the Efficacy of Imeglimin in Individuals With Type 2 Diabetes Mellitus: An Exploratory Study

Naoki Wada  1   2 , Takaaki Murakami  1   2 , Muhammad Fauzi  1 , Kentaro Sakaki  1 , Shinobu Oshima  3 , Yoshihito Shimada  3 , Kanae Asai  3 , Ayako Oshima  3 , Satoko Nomura  3 , Erina Joo  3 , Michiko Mori  3 , Ryoko Fujiwara  3 , Kenichiro Shide  3 , Keiko Wada  3 , Daisuke Yabe  1 , Nobuya Inagaki  4 , Norio Harada  1   5
Affiliations

Elevated Serum Growth Differentiation Factor 15 Levels as a Potential Biomarker of the Efficacy of Imeglimin in Individuals With Type 2 Diabetes Mellitus: An Exploratory Study

Naoki Wada et al. J Clin Med Res. 2024 Oct.

Abstract

Background: The aim of the present study was to conduct a prospective observational study to explore the effects of imeglimin on systemic energy metabolism/body composition and to identify potential mitochondria-related biomarkers of the efficacy of the drug in clinical settings.

Methods: In this prospective observational study, 16 participants with type 2 diabetes mellitus in the diabetes clinic of Kyoto University Hospital were enrolled. Individuals were started on imeglimin as monotherapy or add-on therapy.

Results: After 3 months under imeglimin treatment, there was no significant change in basal metabolism or body composition. However, serum levels of growth differentiation factor 15 (GDF15) were higher while those of serum fibroblast growth factor 21 and urine 8-hydroxy-2'-deoxyguanosine were not changed. Additional in vitro examination revealed that imeglimin induces GDF15 protein release from human hepatocytes.

Conclusions: Three-month imeglimin treatment increased serum GDF15 levels in clinical type 2 diabetes mellitus patients along with little change in basal metabolism or body composition, suggesting GDF15 as a potential marker for the efficacy of imeglimin.

Keywords: Diabetes mellitus; GDF15; Imeglimin.

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Conflict of interest statement

None to declare.

Figures

Figure 1
Figure 1
Correlation between Δgrowth differentiation factor 15 (GDF15) and Δglycoalbumin (GA), Δbody mass index (BMI), diabetes history, baseline HbA1c, baseline GA, baseline BMI. Correlation between ΔGDF15 and each parameter is shown as “r”. ΔGDF15 vs. each parameter, *P < 0.05. ns: not significant; HbA1c: glycated hemoglobin.
Figure 2
Figure 2
GDF15 released from imeglimin-treated HepG2 cells. Control (n = 3), 1 µg/mL imeglimin-treated (n = 3), 2 µg/mL imeglimin-treated HepG2 cells (n = 3). Data are mean ± SD. Control vs. imeglimin-treated, *P < 0.05, ns: not significant; SD: standard deviation.
See this image and copyright information in PMC

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