ArticlePloS one2021
Imeglimin amplifies glucose-stimulated insulin release from diabetic islets via a distinct mechanism of action.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Imeglimin systematic review: a novel therapeutic approach for type 2 diabetes-unveiling benefits on β-cell function, insulin sensitivity, and potential long-term glycaemic control (HbA1c).European journal of clinical pharmacology · 2025Pooled it
- Efficacy, safety and tolerability of imeglimin in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.Journal of diabetes investigation · 2023Pooled it
- Durability and Safety of Imeglimin as an Add-On to DPP-4 Inhibitors in Japanese Type 2 Diabetes: The 104-Week FAMILIAR Trial.Diabetes, obesity & metabolism · 2026Trial
- Dual action of imeglimin on insulin secretion and sensitivity in type 2 diabetes.Diabetes, obesity & metabolism · 2026Trial
- Differential effects of imeglimin and metformin on insulin and incretin secretion-An exploratory randomized controlled trial.Diabetes, obesity & metabolism · 2025Trial
- Imeglimin may affect hemoglobin A1c accuracy via prolongation of erythrocyte lifespan in patients with type 2 diabetes mellitus: insights from the INFINITY clinical trial.Frontiers in endocrinology · 2025Trial
- Effect of Imeglimin, a Novel Anti-Diabetic Agent, on Insulin Secretion and Glycemic Variability in Type 2 Diabetes Treated with DPP-4 Inhibitor: A 16-Week, Open Label, Pilot Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Trial
- Factors contributing to the clinical effectiveness of imeglimin monotherapy in Japanese patients with type 2 diabetes mellitus.Journal of diabetes investigation · 2024Trial
- Phase 2 trial with imeglimin in patients with Type 2 diabetes indicates effects on insulin secretion and sensitivity.Endocrinology, diabetes & metabolism · 2022Trial
- Pharmacokinetics of Imeglimin in Caucasian and Japanese Healthy Subjects.Clinical drug investigation · 2022Trial
- 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, obesity & metabolism · 2022Trial
- 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, obesity & metabolism · 2022Trial
- Effects of imeglimin on liver enzymes and body composition in patients with MASLD and type 2 diabetes: a pilot study.Diabetology international · 2026Article
- Imeglimin-Associated Temporal Changes in γ-Glutamyl Transferase and Total Cholesterol: A Post Hoc Exploratory Analysis of the INFINITY Study.Journal of personalized medicine · 2026Article
- Imeglimin Treatment May Improve Whole-Blood Fluidity and Influence Hemorheology in Patients with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the INFINITY Study.Journal of personalized medicine · 2026Article
- Long-Term Glycemic and Metabolic Profiles Observed During Imeglimin Therapy in Japanese Patients With Type 2 Diabetes Mellitus.Endocrinology, diabetes & metabolism · 2026Observational
- Characterization of extracellular and membrane potentials in imeglimin-treated islets.Journal of diabetes investigation · 2026Article
- Effect of metformin dose reduction versus continuation at imeglimin initiation on glycemic control in type 2 diabetes: a retrospective real-world analysis.Acta diabetologica · 2026Article
- Molecular Mechanisms and Clinical Evidence Supporting the Four Pillars of Therapy in Diabetic Kidney Disease: Emerging Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- O-Acetyl-Serine Supplementation Enhances Insulin Secretion and Improves Postprandial Glycaemia in Lean and Prediabetic Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic islet β-cell dysfunction is characterized by defective glucose-stimulated insulin secretion (GSIS) and is a predominant component of the pathophysiology of diabetes. Imeglimin, a novel first-in-class small molecule tetrahydrotriazine drug candidate, improves glycemia and GSIS in preclinical models and clinical trials in patients with Type 2 diabetes; however, the mechanism by which it restores β-cell function is unknown. Here, we show that imeglimin acutely and directly amplifies GSIS in islets isolated from rodents with Type 2 diabetes via a mode of action that is distinct from other known therapeutic approaches. The underlying mechanism involves increases in the cellular nicotinamide adenine dinucleotide (NAD+) pool-potentially via the salvage pathway and induction of nicotinamide phosphoribosyltransferase (NAMPT) along with augmentation of glucose-induced ATP levels. Further, additional results suggest that NAD+ conversion to a second messenger, cyclic ADP ribose (cADPR), via ADP ribosyl cyclase/cADPR hydrolase (CD38) is required for imeglimin's effects in islets, thus representing a potential link between increased NAD+ and enhanced glucose-induced Ca2+ mobilization which-in turn-is known to drive insulin granule exocytosis. Collectively, these findings implicate a novel mode of action for imeglimin that explains its ability to effectively restore-β-cell function and provides for a new approach to treat patients suffering from Type 2 diabetes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.