Rationale and Design of the Study to Investigate the Metabolic Action of Imeglimin on Patients with Type 2 Diabetes Mellitus (SISIMAI)

Tsubasa Tajima; Hideyoshi Kaga; Naoaki Ito; Toshiki Kogai; Hitoshi Naito; Saori Kakehi; Satoshi Kadowaki; Yuya Nishida; Ryuzo Kawamori; Yoshifumi Tamura; Hirotaka Watada

doi:10.1007/s13300-024-01655-x

Rationale and Design of the Study to Investigate the Metabolic Action of Imeglimin on Patients with Type 2 Diabetes Mellitus (SISIMAI)

Diabetes Ther. 2024 Sep 30. doi: 10.1007/s13300-024-01655-x. Online ahead of print.

Authors

Tsubasa Tajima¹, Hideyoshi Kaga², Naoaki Ito¹, Toshiki Kogai¹, Hitoshi Naito¹, Saori Kakehi³, Satoshi Kadowaki¹, Yuya Nishida¹, Ryuzo Kawamori^{1

3}, Yoshifumi Tamura^{1

3

4}, Hirotaka Watada^{1

3}

Affiliations

¹ Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
² Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. hkaga@juntendo.ac.jp.
³ Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
⁴ Sports Medicine and Sportology, Juntendo University Graduate School of Medicine, Tokyo, Japan.

PMID: 39347897
DOI: 10.1007/s13300-024-01655-x

Abstract

Introduction: Imeglimin is a first-in-class, novel, oral glucose-lowering agent for the treatment of type 2 diabetes mellitus. The efficacy and safety of imeglimin as an antidiabetic agent have been investigated in clinical trials. However, its metabolic effects in humans have not yet been fully elucidated.

Methods: The Study to InveStIgate the Metabolic Action of Imeglimin on patients with type 2 diabetes mellitus (SISIMAI) is a single-arm intervention study. In this study, we have recruited 25 patients with type 2 diabetes to receive 2000 mg/day imeglimin for 20 weeks. We perform a 75-g oral glucose tolerance test (OGTT) with double-glucose tracers, a two-step hyperinsulinemic-euglycemic clamp with glucose tracer, ectopic fat measurement by proton magnetic resonance spectroscopy, visceral/subcutaneous fat area measurement by magnetic resonance imaging, muscle biopsy, and evaluation of fitness level by cycle ergometer before and after imeglimin administration.

Planned outcomes: The primary outcome is the change in area under the curve of glucose levels during the OGTT after 20 weeks of imeglimin treatment. We also calculate the endogenous glucose production, rate of oral glucose appearance, and rate of glucose disappearance from the data during the 75-g OGTT and compare them between pre- and post-treatment. Additionally, we will compare other parameters, such as the changes in tissue-specific insulin sensitivity, ectopic fat accumulation, visceral/subcutaneous fat area accumulation, and fitness level between each point. This is the first study to investigate the organ-specific metabolic action of imeglimin in patients with type 2 diabetes mellitus using the 75-g OGTT with the double tracer method. The results of this study are expected to provide useful information for drug selection based on the pathophysiology of individual patients with type 2 diabetes mellitus.

Trial registration: jRCTs031210600.

Keywords: Ectopic fat; Fitness level; Imeglimin; Insulin secretion; Insulin sensitivity.