Twymeeg (imeglimin) / Poxel SA, Roivant, Sumitomo Pharma - LARVOL DELTA

Imeglimin provides dual hepatic and skeletal muscle protection in experimental MASH-associated sarcopenia. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "Imeglimin attenuated experimental MASH-associated muscle atrophy through coordinated improvement of hepatic function, mitochondrial homeostasis, anabolic signaling, and proteostasis without detectable changes in fasting glucose or insulin levels. These findings support further evaluation of imeglimin as a potential therapy for MASH-associated sarcopenia."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Muscular Atrophy • Sarcopenia • FBXO32 • FOXO3 • IGF1 • IL6 • NAMPT

Imeglimin halts cyclophosphamide-induced ovarian injury: a dual modulation of TLR4/NF-κB/NLRP3-driven inflammation and AMPK/SIRT1/PGC-1α pathways. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Imeglimin attenuates CPA-induced premature ovarian insufficiency via inhibition of oxidative, inflammatory, and pyroptotic damage and p-AMPK/SIRT1/PGC-1α activation, as evidenced by preservation of ovarian structural integrity, follicular architecture, and endocrine markers. These findings highlight its potential as a candidate for chemotherapy-associated ovarian protection, pending further validation through direct fertility outcome studies."

IO biomarker • Journal • Inflammation • Oncology • Women's Health • BAX • BCL2 • CASP3 • IL18 • IL1B • MYD88 • NLRP3 • TLR4 • TNFA • TXNIP

Repurposing imeglimin to treat MASH-associated liver fibrosis by targeting the HSC-VNUT-ATP secretory axis: evidence from cell-specific knockout models (EASD 2026) - "Imeglimin is a first-in-class oral antidiabetic agent derived from metformin...Mechanistically, imeglimin (10 µM) directly inhibited intravesicular ATP accumulation and subsequent secretion from HSCs, mimicking the effects of the VNUT inhibitor clodronate... Our findings reveal that imeglimin acts as a "dual-action" agent by improving hepatocellular metabolism and directly suppressing fibrogenesis through inhibition of VNUT-mediated ATP secretion in HSCs. This study provides a novel mechanistic insight into the clinical benefits of imeglimin for treating advanced MASH-associated fibrosis."

Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Mitochondrial redox modulation in newly diagnosed type 2 diabetes: a randomised controlled trial comparing imeglimin versus metformin monotherapy (EASD 2026) - "In treatment-naive T2DM, imeglimin and metformin achieve equivalent short-term glycemic control but exert diametrically opposite effects on mitochondrial redox status: imeglimin restores the plasma pyruvate/lactate ratio toward a more oxidized, metabolically favorable state, while metformin suppresses it, consistent with their contrasting mechanisms at mitochondrial complex I. These findings support the concept of mitochondrial phenotype-guided antidiabetic drug selection in newly diagnosed T2DM and establish the pyruvate/lactate ratio as a viable pharmacodynamic endpoint for future precision diabetology trials."

Clinical • Monotherapy • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Imeglimin improves mitochondrial quality and protects against lipopolysaccharide-induced acute lung injury by enhancing TXNIP promoter methylation. (PubMed, Biomed Pharmacother) - "Comparative analyses with seven other hypoglycemic agents demonstrated that imeglimin conferred the lowest mortality rate and hypoglycemia incidence in ALI mice, underscoring its superior therapeutic efficacy and safety. Collectively, these results indicate that imeglimin confers protection against LPS-induced ALI by promoting TXNIP promoter methylation, silencing TXNIP expression, enhancing mitochondrial quality control, and attenuating oxidative stress and inflammation, thereby improving survival outcomes and positioning imeglimin as a promising therapeutic candidate for ALI management."

Journal • Acute Lung Injury • Hypoglycemia • Inflammation • Respiratory Diseases • DNMT3B • IL6 • TXNIP

Imeglimin-Associated Temporal Changes in γ-Glutamyl Transferase and Total Cholesterol: A Post Hoc Exploratory Analysis of the INFINITY Study. (PubMed, J Pers Med) - " γ-GTP levels showed a significant decrease during imeglimin treatment and increased during the post-treatment observation period in patients with T2DM. Exploratory analyses identified an association between changes in γ-GTP and total cholesterol; however, these findings should be interpreted cautiously and require confirmation in prospective studies with prespecified endpoints."

Journal • Retrospective data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

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. (PubMed, J Pers Med) - " In this exploratory post hoc analysis, imeglimin treatment was associated with reduced whole-blood passage time measured using the MC-FAN system, suggesting improved whole-blood fluidity in patients with T2D. The clinical and mechanistic significance of this observation requires confirmation in future controlled prospective studies incorporating direct assessments of erythrocyte rheology and microvascular function."

Journal • Retrospective data • Diabetes • Hematological Disorders • Metabolic Disorders • Type 2 Diabetes Mellitus

Eco-friendly stability-indicating HPLC method development, validation, and LC-MS-based characterization of degradation products of the polar drug imeglimin. (PubMed, J Pharm Sci) - "Consequently, the probable root cause of DP4 formation in the drug product was identified through an experiment involving the enzymatic neutralization of hydrogen peroxide (H2O2). Following ICH Q2(R2) guidelines, the developed method demonstrated suitability for quality control testing of the IMG drug substance and the finished tablet product."

Journal • Diabetes

Real-world effectiveness and safety of imeglimin in Japanese patients with type 2 diabetes: a retrospective observational study. (PubMed, Diabetol Int) - "These findings suggest that add-on imeglimin may contribute to improved glycemic control in patients able to continue treatment without regimen modification. The online version contains supplementary material available at 10.1007/s13340-026-00924-3."

Journal • Observational data • Real-world evidence • Retrospective data • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Hepatoprotective Effects of Imeglimin Are Associated With Preserved Mitochondrial Bioenergetics and Reduced Oxidative Stress in a Murine Cholestasis Model. (PubMed, Hepatol Res) - "Imeglimin exerted hepatoprotective effects on BDL-operated mice, which are associated with preserved mitochondrial bioenergetic function and reduced oxidative stress."

Journal • Preclinical • Cholestasis • Fibrosis • Hepatology • Immunology • Inflammation • ACTA2 • COL1A1 • IL1B • IL6

Imeglimin in Indian Adults with Type 2 Diabetes: A Prospective Multicenter Real-world Cohort Study of Prescription Patterns, Glycemic Change, and Safety. (PubMed, J Assoc Physicians India) - "In routine clinical practice, the initiation of imeglimin among Indian adults with T2D was associated with clinically meaningful reductions in HbA1c, fasting plasma glucose, and postprandial glucose over a 6-month period, alongside a favorable safety profile. These real-world findings support the clinical utility and tolerability of imeglimin as an effective therapeutic option for glycemic management in this population. Future randomized controlled trials with extended follow-up are warranted to establish definitive causal treatment effects and evaluate long-term clinical outcomes."

Journal • Observational data • Real-world evidence • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Imeglimin in Type 2 Diabetes Mellitus: Expert Opinions and Consensus in Indian Context. (PubMed, J Assoc Physicians India) - "The article is timely and informative, particularly in view of the increasing complexity of diabetes management in India. The debate around the novel mechanism of imeglimin, which addresses both insulin resistance and mitochondrial dysfunction through mitochondrial routes, is well summarized and is in line with the increasing emphasis on preserving the function of the beta cell.1."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Imeglimin Attenuates Skeletal Muscle Atrophy in Mouse Models of Obesity and Ageing. (PubMed, J Cachexia Sarcopenia Muscle) - "Imeglimin attenuates skeletal muscle atrophy in obesity and ageing, accompanied by coordinated suppression of stress- and inflammation-associated transcriptional programmes. These findings indicate that pharmacological regulation of mitochondrial stress responses influences skeletal muscle vulnerability under chronic metabolic stress and identify skeletal muscle as a previously underappreciated target of imeglimin action."

Journal • Preclinical • Genetic Disorders • Inflammation • Metabolic Disorders • Muscular Atrophy • Obesity • Sarcopenia

Imeglimin confers protection against intestinal ischemia/reperfusion injury in rats through AMPK-dependent inhibition of NF-κB/NLRP3 inflammasome signaling and mitigation of oxidative stress and apoptosis. (PubMed, Inflammopharmacology) - "IMEG exerts a protective effect against intestinal I/R injury through its antioxidant, anti-inflammatory, and anti-apoptotic properties (Fig. 1)."

IO biomarker • Journal • Preclinical • Cardiovascular • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Reperfusion Injury • AMPK • BAX • BCL2 • CASP3 • IL1B • NLRP3

AQbD-Based Development and Optimization of a Stability-Indicating RP-HPLC Method for Imeglimin With Integration of Lean Six Sigma Principles. (PubMed, Biomed Chromatogr) - "HR-MS and FTIR studies indicated that N-dealkylation and N-demethylation were possible degradation pathways. The greenness assessment of the developed method was carried out using AGREE, GAPI, BAGI, and CLICK indices."

Journal

Short-Term Glycemic Outcomes Associated with Imeglimin Use Among Patients with Type 2 Diabetes Mellitus: A Prospective Observational Study. (PubMed, Drug Des Devel Ther) - "Most metabolic parameters remained stable, with a modest improvement in HDL cholesterol observed. Further large-scale studies with longer follow-up are needed to confirm these findings."

Journal • Observational data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Durability and Safety of Imeglimin as an Add-On to DPP-4 Inhibitors in Japanese Type 2 Diabetes: The 104-Week FAMILIAR Trial. (PubMed, Diabetes Obes Metab) - "Imeglimin added to DPP-4 inhibitors appeared to improve glycemic control for 104 weeks, without clear attenuation. The combination was well-tolerated with a low risk of hypoglycemia even in elderly patients. The long-term effect may be associated with improvements in insulin sensitivity."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Insulin-reducing effect of adding imeglimin to ongoing dipeptidyl peptidase-4 inhibitor therapy with multiple daily insulin injections (INSPIRE study). (PubMed, J Diabetes Investig) - "Adding imeglimin to DPP-4i significantly reduced insulin dosage, even in patients with low insulin secretory capacity. This combination may represent a useful therapeutic option for Japanese patients with T2D treated with MDI."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Bioequivalence Study to Compare Imeglimin HCl 500 mg Film Coated Tablets Versus Twymeeg Tablets 500 mg (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Humanis Sagl?k Anonim Sirketi

New P1 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Imeglimin as a Replacement Therapy for Metformin in Patients With Type 2 Diabetes Mellitus Experiencing Metformin Intolerance: A Retrospective Observational Study. (PubMed, Cureus) - "Conclusion Imeglimin demonstrated meaningful improvements in glycemic control, with a favorable safety and tolerability profile in metformin-intolerant patients with T2DM. These findings support the use of imeglimin as an effective and well-tolerated alternative option for metformin in patients with T2DM."

Journal • Observational data • Retrospective data • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Long-Term Glycemic and Metabolic Profiles Observed During Imeglimin Therapy in Japanese Patients With Type 2 Diabetes Mellitus. (PubMed, Endocrinol Diabetes Metab) - "In a real-world setting, long-term imeglimin therapy was associated with sustained glycemic improvement and early as well as sustained numerical changes in an insulin secretion index without an increase in overall treatment intensity."

Journal • Observational data • Retrospective data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Enantioselective separation of imeglimin API on novel immobilized cellulose-tris(3-chloro-5-methyl phenyl carbamate) by HPLC and preparative purification by SFC techniques. (PubMed, Anal Methods) - "The method was successfully validated in accordance with ICH guidelines and applied to the analysis of multiple batches of imeglimin hydrochloride bulk drug. Furthermore, the applicability of the newly introduced CSP was demonstrated with several active pharmaceutical ingredients, providing excellent enantiomeric resolution and superior performance compared with previously reported chiral HPLC methods."

Journal

Imeglimin enhances GLUT4-mediated glucose uptake and is more effective than metformin in 3T3-L1 adipocytes. (PubMed, Biochem Biophys Res Commun) - "Imeglimin, a novel oral antidiabetic agent derived from metformin, improves insulin secretion and sensitivity in patients with type 2 diabetes. Further, pharmacological inhibition studies demonstrated that imeglimin-induced glucose uptake was unaffected by AMPK inhibition but attenuated by inhibition of phosphoinositide 3-kinase, Akt, or protein kinase C. Additionally, the PI3K inhibitor Ly294002 suppressed imeglimin-induced GLUT4 accumulation at the plasma membrane. These findings identify adipocytes as a relevant cellular target of imeglimin and support, at least in part, the involvement of PI3K-dependent GLUT4 regulation in facilitating glucose transport, which may contribute to favorable effects of imeglimin on adipose tissue glucose metabolism in vivo."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • AMPK • SLC2A1 • SLC2A4

Clarifying metformin exposure when interpreting glycemic responses after imeglimin initiation. (PubMed, Acta Diabetol) - No abstract available

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Chronic infection and metabolic stress: a converging axis driving hypertension and MASLD outcomes. (PubMed, Am J Hypertens) - "Pharmacological AMPK activation, exemplified by imeglimin targeting presenilin enhancer-2, highlights the translational potential of therapies addressing hepatic and vascular injury simultaneously. This perspective summarizes clinical and mechanistic evidence supporting an integrated, systems-based framework in which chronic infection and metabolic stress converge along a shared axis to drive hypertension and MASLD. It underscores the need to incorporate metabolic regulation, cardiovascular risk modification, and selected infectious determinants into future risk stratification models and therapeutic strategies."

Journal • Cardiovascular • Fibrosis • Hepatology • Hypertension • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pulmonary Arterial Hypertension