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; Takaaki Murakami; Muhammad Fauzi; Kentaro Sakaki; Shinobu Oshima; Yoshihito Shimada; Kanae Asai; Ayako Oshima; Satoko Nomura; Erina Joo; Michiko Mori; Ryoko Fujiwara; Kenichiro Shide; Keiko Wada; Daisuke Yabe; Nobuya Inagaki; Norio Harada

doi:10.14740/jocmr6031

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

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

Authors

Naoki Wada^{1

2}, Takaaki Murakami^{1

2}, Muhammad Fauzi¹, Kentaro Sakaki¹, Shinobu Oshima³, Yoshihito Shimada³, Kanae Asai³, Ayako Oshima³, Satoko Nomura³, Erina Joo³, Michiko Mori³, Ryoko Fujiwara³, Kenichiro Shide³, Keiko Wada³, Daisuke Yabe¹, Nobuya Inagaki⁴, Norio Harada^{1

5}

Affiliations

¹ Department of Diabetes, Endocrinology, and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
² These authors contributed equally to this work.
³ Department of Metabolism and Clinical Nutrition, Kyoto University Hospital, Kyoto, Japan.
⁴ Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, Osaka, Japan.
⁵ Department of Endocrinology and Metabolism, School of Medical Sciences, University of Fukui, Japan.

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.

Grants and funding

NI received joint research grants from Daiichi Sankyo, Terumo, and Drawbridge Health, received speaker honoraria from Kowa, MSD, Astellas Pharma, Novo Nordisk Pharma, Ono, Nippon Boehringer Ingelheim, Takeda, and Mitsubishi Tanabe Pharma, and received scholarship grants from Kissei, Sanofi, Daiichi-Sankyo, Mitsubishi Tanabe, Takeda, Japan Tobacco, Kyowa Kirin, Sumitomo Pharma, Astellas Pharma, MSD, Eli Lilly Japan, Ono, Sanwa Kagaku Kenkyusho, Nippon Boehringer Ingelheim, Novo Nordisk Pharma, Novartis Pharma, Teijin Pharma, and Life Scan Japan. DY has received consulting or speaker fees from Sumitomo Pharma Co., Ltd., Eli Lilly Japan K.K., MSD K.K., Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim Co., Ltd., and Tanabe Mitsubishi Pharma, Co., Ltd., and clinically commissioned/joint research grants from Taisho Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Arklay Co. Ltd. and Nippon Boehringer Ingelheim Co., Ltd. NH received scholarship grants from Mitsubishi Tanabe Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., and Sanofi K.K. TM received a joint research grant from Sumitomo Pharma. The remaining authors have no conflicts of interest to disclose.