1888-LB: Differential Effect of Imeglimin Compared with Metformin on Insulin and Incretin Secretion—A Randomized Controlled Trial
Authors: USUI RYOTA , HAMAMOTO YOSHIYUKI , IMURA MASAHIRO , OMORI YASUHIRO , KUROTOBI YURI , KUWATA HITOSHI , TATSUOKA HISATO , SHIMOMURA KAZUHIRO , MUROTANI KENTA , YAMADA YUICHIRO , SEINO YUTAKA 
Published: June 2024

Background: Imeglimin has related structure to metformin, but several studies have revealed dissimilarities of glucose-lowering mechanisms between the two drugs. Some clinical trials suggest unlike metformin, imeglimin exhibits hypoglycemic effect by enhancing insulin secretion rather than improving insulin resistance. In addition, nothing is known regarding the difference of effect on incretin secretion between two drugs. Therefore, we investigate the effects of imeglimin on insulin and incretin secretion in comparison with metformin in patients with type 2 diabetes.
Method: This was a single center, open-label, randomized controlled trial included drug-naïve patients with type 2 diabetes. Patients were randomized to imeglimin group (IME, 20 patients, 2000mg/day) or metformin group (MET, 21patients, 1000mg/day) and 4h-OGTT was performed before and after 12 and 24weeks.
Result: 20 patients in IME and 20 patients in MET completed the trial. The reduction in HbA1c at 24weeks was similar between IME and MET (7.9±0.1→7.1±0.1(IME), 8.0±0.2→7.1±0.1%(MET)). OGTT exhibited similar decrease in post-challenge blood glucose excursions in both groups. On the other hand, area under the curve of insulin was significantly increased only in IME (30352.1±4523.7→37695.8±5133.4pM x min). Glucagon levels were unchanged. Active GLP-1 levels were significantly increased in both IME and MET (489.6±73.7→917.2±107.4 (IME), 611.7±69.1→854.0±106.3pM x min (MET)). By contrast, active GIP levels were significantly increased only in IME(4718.3±363.7→6332.8±578.3 (IME), 5422.5±617.9→5559.3±529.0pM x min (MET)). Body weight change did not differ between the two groups.
Conclusion: Although imeglimin and metformin demonstrate comparable improvement in glucose tolerance, insulinotropic effect and the effect on incretin secretion is different between imeglimin and metformin suggesting the difference of mechanism underlying their glucose-lowering effect.

Disclosure
R. Usui: None. Y. Hamamoto: Speaker's Bureau; Novo Nordisk A/S. Research Support; Boehringer-Ingelheim, Sumitomo Dainippon Pharma Co., Ltd. M. Imura: None. Y. Omori: None. Y. Kurotobi: None. H. Kuwata: None. H. Tatsuoka: None. K. Shimomura: None. K. Murotani: Speaker's Bureau; AstraZeneca, Daiichi Sankyo, Pfizer Inc., Taiho Pharmaceutical Co. Ltd. Y. Yamada: Speaker's Bureau; Sumitomo Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Teijin Pharma Limited. Y. Seino: Research Support; Eli Lilly and Company, Terumo Corporation, MSD Life Science Foundation, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Arkray Marketing, Novo Nordisk. Speaker's Bureau; GlaxoSmithKline plc, Johnson & Johnson Medical Devices Companies, Sanofi, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited, Boehringer-Ingelheim, Becton, Dickinson and Company.

Funding
Research grants from Sumitomo Pharma