ArticleEndocrinology, diabetes & metabolism2021
The mechanism by which imeglimin inhibits gluconeogenesis in rat liver cells.
Article in Endocrinology, diabetes & metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07436182 (Mitochondrial Redox Modulation in Newly Diagnosed Type 2 Diabetes), which is not on this map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Mitochondrial Redox Modulation in Newly Diagnosed Type 2 Diabetes: A Randomized Controlled Trial Comparing Imeglimin vs. Metformin Monotherapy
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- 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
- 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
- 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
- Effects of imeglimin on liver enzymes and body composition in patients with MASLD and type 2 diabetes: a pilot study.Diabetology international · 2026Article
- The Potential Roles of Oral Hypoglycemic Agents to Modulate Mitochondrial Function in Type 1 Diabetes Mellitus: A Scoping Review.Life (Basel, Switzerland) · 2026Review
- Long-Term Glycemic and Metabolic Profiles Observed During Imeglimin Therapy in Japanese Patients With Type 2 Diabetes Mellitus.Endocrinology, diabetes & metabolism · 2026Observational
- Effects of imeglimin on experimental diabetic neuropathy in streptozotocin-induced diabetic rats.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
- Hydrophilic metformin and hydrophobic biguanides inhibit mitochondrial complex I by distinct mechanisms.Nature structural & molecular biology · 2026Article
- Imeglimin may improve albuminuria associated with partial suppression of inflammatory and fibrotic markers in diabetic kidney disease.Frontiers in pharmacology · 2026Article
- Promoting Drp1-Mediated Mitochondrial Division in Nickel Nanoparticles-Induced Reproductive Toxicity in GC-2 Cells.Nanomaterials (Basel, Switzerland) · 2025Article
- Similarities and differences in the intestinal actions of metformin and imeglimin.Diabetes, obesity & metabolism · 2025Article
- Imeglimin in Patients with an Estimated Glomerular Filtration Rate Less than 45 mL/min per 1.73 mJMA journal · 2025Article
- Imeglimin Alleviates High-Glucose-Induced Bioenergetic and Oxidative Stress Thereby Enhancing Intercellular Adhesion in H9c2 Cardiomyoblasts.International journal of molecular sciences · 2025Article
- The Combination of PPARα Agonist GW7647 and Imeglimin Has Potent Effects on High-Glucose-Induced Cellular Biological Responses in Human Retinal Pigment Epithelium Cells.Bioengineering (Basel, Switzerland) · 2025Article
- Mitochondrial Dysfunction in Diabetes: Shedding Light on a Widespread Oversight.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Review
- Real-world effectiveness and safety of imeglimin: a single-center retrospective cohort study in Japan.Frontiers in clinical diabetes and healthcare · 2025Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aims: To understand the mechanism by which imeglimin (a new oral hypoglycemic agent whose phase 3 development program in Japan has now been completed) decreases hepatic glucose production. Materials and methods: We compared the effect of imeglimin and metformin on glucose production, ATP/ADP ratio, oxygen consumption rate, mitochondrial redox potential and membrane potential in primary rat hepatocytes. Results: We found that both imeglimin and metformin dose-dependently decreased glucose production and the ATP/ADP ratio. Moreover, they both increased mitochondrial redox potential (assessed by mitochondrial NAD(P)H fluorescence) and decreased membrane potential (assessed by TMRM fluorescence). However, contrary to metformin, which inhibits mitochondrial Complex I, imeglimin did not decrease the oxygen consumption rate in intact cells. By measuring the oxygen consumption of in situ respiratory chain as a function of the concentration of NADH, we observed that imeglimin decreased the affinity of NADH for the respiratory chain but did not affect its Vmax (ie competitive inhibition) whereas metformin decreased both the Vmax and the affinity (ie uncompetitive inhibition). Conclusions: We conclude that imeglimin induces a kinetic constraint on the respiratory chain that does not affect its maximal activity. This kinetic constraint is offset by a decrease in the mitochondrial membrane potential, which induces a thermodynamic constraint on the ATPase responsible for a decrease in the ATP/ADP ratio.
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Registered trials
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 OpenQuestion graph.