Imeglimin: the New Kid on the Block

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Hallakou-Bozec S, Vial G, Kergoat M, et al. Mechanism of action of imeglimin: a novel therapeutic agent for type 2 diabetes. Diabetes Obes Metab. 2021;23:664–73. https://doi.org/10.1111/dom.14277.

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Fouqueray P, Leverve X, Fontaine E, Baquié M, Wollheim C, Lebovitz H, Bozec S. Imeglimin—a new oral anti-diabetic that targets the three key defects of type 2 diabetes. J Diab Metabol. 2011;2(126):1–8. https://doi.org/10.4172/2155-6156.1000126.

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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(3):800–10. https://doi.org/10.1111/dom.14285.

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Protective effects of imeglimin and metformin combination therapy on β-cells in db/db male mice Kuniyuki Nishiyama, Masato Ono, Takahiro Tsuno, Ryota Inoue, Ayako Fukunaka, Endocrinology, Volume 164, Issue 8, August 2023, https://doi.org/10.1210/endocr/bqad095

• Dubourg J, Fouqueray P, Thang C, Grouin JM, Ueki K. Efficacy and safety of imeglimin monotherapy versus placebo in Japanese patients with type 2 diabetes (TIMES 1): a double-blind, randomized, placebo-controlled, parallel-group, multicenter phase 3 trial. Diabetes Care. 2021;44(4):952–9. https://doi.org/10.2337/dc20-0763. First phase-3 trial that compared imeglimin as a monotherapy that proved its effectiveness and safety.

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•• 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 patients with type 2 diabetes (TIMES 2): a 52-week, open-label, multicentre phase 3 trial. Diabetes Obes Metab. 2022;24(4):609–19. https://doi.org/10.1111/dom.14613. First phase-3 trial that evaluated effectiveness of imeglimin in combination with other oral anti-diabetic drugs, verifying its potency and safety profile.

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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 3): a randomized, double-blind, placebo-controlled phase 3 trial with a 36-week open-label extension period. Diabetes Obes Metab. 2022;24(5):838–48. https://doi.org/10.1111/dom.14642.

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Oda T, Satoh M, Nagasawa K, Sasaki A, Hasegawa Y, Takebe N, Ishigaki Y. The effects of imeglimin on the daily glycemic profile evaluated by intermittently scanned continuous glucose monitoring: retrospective, single-center, observational study. Diabetes Ther. 2022;13(9):1635–43. https://doi.org/10.1007/s13300-022-01298-w.

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• Awadhesh Kumar Singh, Akriti Singh, Ritu Singh, Anoop Misra, Efficacy and safety of imeglimin in type 2 diabetes: a systematic review and meta-analysis of randomized placebo-controlled trials. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2023 17(2):102710, ISSN 1871-4021. https://doi.org/10.1016/j.dsx.2023.102710. A very thorough article that evaluates imeglimin through systematic analysis and metanalysis, covering all the publications.

•• Ishibashi R, Hirayama K, Watanabe S, Okano K, Kuroda Y, Baba Y, Kanayama T, Ito C, Kasahara K, Aiba S, Iga R, Ohtani R, Inaba Y, Koshizaka M, Maezawa Y, Yokote K (2023) Imeglimin-mediated glycemic control in maternally inherited deafness and diabetes. J Diabetes Investig. 2023. https://doi.org/10.1111/jdi.14085https://doi.org/10.1111/jdi.14085. Unique case report that lends credibility to the role of mitochondria in the pathogenesis of diabetes and to the role of imeglimin in correcting the dysfunction.

Theurey P, Vial G, Fontaine E, Monternier P-A, Fouqueray P, Bolze S, Moller DE, Hallakou-Bozec S. Reduced lactic acidosis risk with imeglimin: comparison with metformin. Physiological Reports. 2022;10:15151. https://doi.org/10.14814/phy2.15151.

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Yanai H, Adachi H, Hakoshima M, Katsuyama H. Glucose-lowering effects of imeglimin and its possible beneficial effects on diabetic complications. Biology. 2023;12:726. https://doi.org/10.3390/biology12050726.

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Yendapally R, Sikazwe D, Kim SS, Ramsinghani S, Fraser-Spears R, Witte AP, La-Viola B. A review of phenformin, metformin, and imeglimin. Drug Dev Res. 2020;81(4):390–401. https://doi.org/10.1002/ddr.21636.

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