Dual Action Mechanism of Insulin Resistance and Insulin Secretion by Imeglimin for Diabetic Treatment
DOI:
https://doi.org/10.17140/DROJ-8-e017Keywords:
Imeglimin; Twymeeg; Trials of imeglimin for efficacy and safety 2 (TIMES 2), Glucose-stimulated insulin secretion (GSIS);, Transient receptor potential melastatin 2 (TRPM2) channel.Abstract
Imeglimin (Twymeeg) is novel oral hypoglycemic agent (OHA) developed in the glimin category. It has dual action mechanisms of
reducing insulin resistance and increasing insulin secretion. Trials of imeglimin for efficacy and safety 1 (TIMES 1), TIMES 2 and
TIMES 3 were performed with significant clinical efficacy. Among them, HbA1c decrease for 52 weeks showed single imeglimin
-0.46%, combined therapy of dipeptidyl peptidase-4i (DPP-4i)-0.92%, Glucagon-like peptide-1 receptor agonists (GLP-1RA)-0.12%
and insulin -0.63%. From physiological and pharmacological points of view, the mechanism may include the enhancement action
of glucose-stimulated insulin secretion (GSIS). For GSIS progress, transient receptor potential melastatin 2 (TRPM2) channel is
activated.
References
Ogurtsova K, Guariguata L, Barengo NC, et al. IDF diabe-tes Atlas: Global estimates of undiagnosed diabetes in adults for 2021. Diabetes Res Clin Pract. 2022; 183: 109118. doi: 10.1016/j. diabres.2021.109118
American Diabetes Association (ADA). Introduction: Stan-dards of medical care in diabetes—2022. Diabetes Care. 2022; 45(Suppl. 1): S1-S2. doi: 10.2337/dc22-SINT
Bando H. Latest trend for standards of medical care in diabe-tes. SunText Rev Endocrine Care. 2022; 1(1): 106. doi: 10.51737/ endocrine.2021.006
American Diabetes Association (ADA) Professional Practice Committee. 9. Pharmacologic approaches to glycemic treatment: Standards of medical care in diabetes—2022. Diabetes Care. 2022; 45(Suppl. 1): S125-S143. doi: 10.2337/dc22-S009
Ishigaki Y, Strizek A, Aranishi T, et al. Glucagon-like peptide-1 receptor agonist utilization in type 2 diabetes in Japan: A retro-spective database analysis (JDDM 57). Diabetes Ther. 2021; 12(1): 345-361. doi: 10.1007/s13300-020-00977-w
Tanaka K, Okada Y, Tokutsu A, Tanaka Y. Real-world effective-ness of liraglutide versus dulaglutide in Japanese patients with type 2 diabetes: A retrospective study. Sci Rep. 2022; 12(1): 154. doi: 10.1038/s41598-021-04149-z
Yendapally R, Sikazwe D, Kim SS, et al. A review of phenfor-Editorial | Volume 8 | Number 1 | Diabetes Res Open J. 2022; 8(1): e1-e3. doi: 10.17140/DROJ-8-e017 min, metformin, and imeglimin. Drug Dev Res. 2020; 81(4): 390- 401. doi: 10.1002/ddr.21636
Giruzzi M. Imeglimin. Clin Diabetes. 2021; 39 (4): 439-440. doi: 10.2337/cd21-0085
Dubourg J, Ueki K, Grouin JM, Fouqueray P. Efficacy and safety of imeglimin in Japanese patients with type 2 diabetes: A 24-week, randomized, double-blind, placebo-controlled, dose-ranging phase 2b trial. Diabetes Obes Metab. 2021; 23: 800-810. doi:
1111/dom.14285 10. Iwatsuki N, Bando H, Okada M. Pharmacological characteris-tic of imeglimin (Twymeeg) for dual mechanism to insulin secre-tion and resistance. SunText Rev Pharm Sci. 2022; 3(1): 113. doi: 10.51737/2766-5232.2022.013
Okada M, Bando H, Iwatsuki N, Ogawa T, Sakamoto K. Clini-cal efficacy of imeglimin (Twymeeg) for elderly patient with type 2 diabetes mellitus (T2DM). Asp Biomed Clin Case Rep. 2022; 5(1): 33-37. doi: 10.36502/2022/ASJBCCR.6259
Dubourg J, Fouqueray P, Thang C, Grouin JM, Ueki K. Effi-cacy and safety of imeglimin monotherapy versus placebo in Japa-nese patients with type 2 diabetes (TIMES 1): A double-blind, randomized, placebo-controlled, parallel-group, multicenter phase 3 trial. Diabetes Care. 2021; 44(4): 952-959. doi: 10.2337/ dc20-0763
Dubourg J, Fouqueray P, Quinslot D, Grouin JM, Kaku K. Long-term safety and efficacy of imeglimin as monotherapy or in combination with existing antidiabetic agents in Japanese pa-tients with type 2 diabetes (TIMES 2): A 52-week, open-label, multicentre phase 3 trial. Diabetes Obes Metab. 2021. doi: 10.1111/ dom.14613
Reilhac C, Dubourg J, Thang C, Grouin JM, Fouqueray P, Watada H. Efficacy and safety of imeglimin add-on to insulin monotherapy in Japanese patients with type 2 diabetes (TIMES Submit your article to this journal | https://openventio.org/submit-manuscript/ Editorial | Volume 8 | Number 1 | Bando H 3): A randomized, double-blind, placebo-controlled phase 3 trial with a 36-week open-label extension period. Diabetes Obes Metab. 2022. doi: 10.1111/dom.14642
Pirags V, Lebovitz H, Fouqueray P. Imeglimin, a novel glimin oral antidiabetic, exhibits a good efficacy and safety profile in type 2 diabetic patients. Diabetes Obes Metab. 2012; 14: 852-858. doi: 10.1111/j.1463-1326.2012.01611.x
Funazaki S, Yoshida M, Yamada H, et al. A novel mechanism of imeglimin-mediated insulin secretion via the cADPR-TRP channel pathway. J Diabetes Investig. 2021. doi: 10.1111/jdi.13669
Hallakou-Bozec S, Vial G, Kergoat M, et al. Mechanism of ac-tion of imeglimin: A novel therapeutic agent for type 2 diabetes. Diabetes Obes Metab. 2021; 23: 664-673. doi: 10.1111/dom.14277
Funazaki S, Yoshida M, Yamada H, et al. A novel mecha-nism of imeglimin-mediated insulin secretion via the cADPR-TRP channel pathway. J Diabetes Investig. 2022; 13(1): 34-41. doi: 10.1111/jdi.13669
Tomita Y, Hansson E, Mazuir F, et al. Imeglimin population pharmacokinetics and dose adjustment predictions for renal im-pairment in Japanese and Western patients with type 2 diabetes. Clin Transl Sci. 2021. doi: 10.1111/cts.13221
Chevalier C, Dubourg J, Bolze S, Fouqueray P. Pharmacokinet-ics of imeglimin in subjects with moderate hepatic impairment. Clin Pharmacokinet. 2021; 60(4):85-490. doi: 10.1007/s40262-020- 00948-1
Abdelhaleem IA, Salamah HM, Alsabbagh FA, et al. Efficacy and safety of imeglimin in patients with type 2 diabetes melli-tus: A systematic review and meta-analysis of randomized clinical trials. Diabetes Metab Syndr. 2021; 15(6): 102323. doi: 10.1016/j. dsx.2021.102323 e3
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content published in Diabetes Research (DR) is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license allows anyone to copy, distribute, transmit, and adapt the work — including for commercial purposes — provided appropriate credit is given to the original author(s) and source.
