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

The Efficacy of Imeglimin and Metformin on Insulin Sensitivity and Secretion Using Oral Minimal Model—Subanalysis of a Randomized Controlled Trial (ADA 2025) - "Imeglimin enhanced both insulin secretion and sensitivity regardless of patients' background, while metformin primarily improved insulin sensitivity and exerted heterogeneous effects on beta-cell function, highlighting the distinct mechanisms of action between the two drugs."

Clinical • Late-breaking abstract • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Adenylosuccinate Mediates Imeglimin-Induced Proliferative and Antiapoptotic Effects in β-Cells (ADA 2025) - "Taken together, these findings suggest that chronic treatment with imeglimin promotes β-cell proliferation and survival partly through an increase in S-AMP production."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Imeglimin May Improve Inflammation and Fibrosis in Diabetic Kidney Disease (ADA 2025) - "Imeglimin could improve albuminuria in DKD via anti-inflammation and anti-fibrotic actions and may prevent from the progression of DKD."

Metabolic Disorders • Type 2 Diabetes Mellitus • ICAM1 • IL1B • NLRP3 • TLR4 • TNFA • VCAM1

Age-Related and Sex Differences in the Effectiveness of Novel Antidiabetic Agent Imeglimin in Japanese Type 2 Diabetes Patients (ADA 2025) - "In this study, we investigated differences in the effectiveness of imeglimin according to age, and by sex. Age had no impact on the effectiveness of imeglimin in the male group. In the female group, on the other hand, the reduction in HbA1c levels diminished with age, and the decreases in both TC and non-HDL-C were enhanced with age."

Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Attempts to Identify Predictors of Glycemic Control with Imeglimin—Machine Learning Analysis Using Clinical Trial Data (ADA 2025) - "Machine learning algorithms were shown to provide a hypothetical, unbiased approach for predicting treatment success in T2D, enhancing the search for predictors. The integration of machine learning in healthcare could empower clinicians to utilize relevant data for optimal and personalized patient care."

Clinical • Machine learning • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Effect of Imeglimin on Periodontitis in Streptozotocin-Induced Diabetic Rats (ADA 2025) - "These results suggest that mitochondrial dysfunction may be involved in the mechanism of periodontal exacerbation in diabetes mellitus."

Preclinical • Diabetes • Metabolic Disorders • Osteoporosis • TNFA

Therapeutic Potential of Imeglimin for Diabetic Neuropathy—Neuroprotective Effects in Type 1 Diabetic Rats (ADA 2025) - "These findings from STZ-induced diabetic rats indicate the therapeutic potential of imeglimin for diabetic neuropathy."

Preclinical • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Type 1 Diabetes Mellitus

Imeglimin in Type 2 Diabetes Mellitus: Expert Opinions and Consensus in Indian Context. (PubMed, J Assoc Physicians India) - "This consensus paper presents the experts' opinion of their real-world clinical experiences on imeglimin treatment, its clinical efficacy, safety and their recommendations for better management of T2DM."

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

Imeglimin improves hyperglycemia and hypoglycemia-induced cell death and mitochondrial dysfunction in immortalized adult mouse Schwann IMS32 cells. (PubMed, J Diabetes Investig) - "Fluctuations in glucose levels impair mitochondrial function in Schwann cells, contributing to peripheral nerve damage in diabetic neuropathy. Imeglimin demonstrated protective effects by alleviating mitochondrial dysfunction and preventing apoptosis signaling. These findings suggest the potential application of imeglimin in preventing and treating diabetic neuropathy; however, the clinical implications require further investigation."

Journal • Preclinical • Diabetes • Diabetic Neuropathy • Hypoglycemia • Metabolic Disorders • Pain

A case of mitochondrial diabetes mellitus with successful therapeutic response following the initiation of imeglimin. (PubMed, Intractable Rare Dis Res) - "After starting imeglimin, the patient's blood glucose levels stabilized, and he continues treatment. While the molecular target of imeglimin remains unknown, it is possible that the drug may offer significant benefits for patients with mitochondrial diabetes mellitus."

Journal • Diabetes • Metabolic Disorders

Different effects of imeglimin and metformin on insulin secretion and the mitochondrial metabolism of isolated pancreatic islands. (DDG 2025) - "Imeglimin, like Metformin, influences the mitochondrial respiratory chain, whereby both substances lead to a backlog of reducing equivalent NADH and FADH2. The increase in the glucose-stimulated ATP/ADP ratio by imeglimin can be caused by a reduced proton leak of the inner mitochondria membrane, which can also lead to an increased river through the respiratory chain to an increased ATP synthesis in the complex V."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Verification of the Short-Term Impact of Imeglimin on Liver Fibrosis Markers Stratified by Liver Fibrosis Risk in Patients With Type 2 Diabetes. (PubMed, Cureus) - "ΔFIB-4 was negatively correlated with baseline FIB-4 and Triglycerides (TG), and positively correlated with Δγ-glutamyl transpeptidase (γ-GTP). Conclusions The short-term effects of imeglimin on FIB-4 and APRI in patients with T2DM may be more pronounced in patients with higher baseline FIB-4 levels."

Journal • Diabetes • Fibrosis • Immunology • Liver Cirrhosis • Metabolic Disorders • Type 2 Diabetes Mellitus

Poxel Reports Consolidated Revenue for the First Quarter 2025 and Provides Corporate Update (Poxel Press Release) - "TWYMEEG consolidated gross sales in Japan for Sumitomo Pharma Fiscal Year 20241 achieved JPY 7.6 billion (EUR 47,2 million), in line with Sumitomo Pharma’s latest guidance. Sumitomo Pharma forecast for TWYMEEG’s FY 20254 of JPY 11.2 billion (EUR 69,4 million2), representing a 47% increase over FY 2024 sales....Regulatory approval on April 8, 2025, by the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan enabling Sumitomo Pharma to immediately start promoting the use of TWYMEEG (Imeglimin) in type 2 diabetic patients with moderate to severe renal impairment....This regulatory milestone builds on the recently granted patent (n°7635474) by the Japanese Patent Office to Poxel covering the use of Imeglimin in type 2 diabetic patients with moderate to severe renal impairment until 2039, strengthening TWYMEEG’s patent portfolio in Japan and protecting its use in this population."

Japan approval • Sales • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and safety of imeglimin, a novel oral agent in the management of type 2 diabetes mellitus: a systematic review and meta-analysis. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Imeglimin is an effective and safe option for T2DM, particularly for improving glycemic control and β-cell function. Further studies in diverse populations are needed to confirm these findings. Trial Registration: PROSPERO (CRD42024564036)."

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

Imeglimin and DPP-4 inhibitors: A promising therapeutic strategy for type 2 diabetes individuals with reduced insulin secretion. (PubMed, Diabetes Obes Metab) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy of Imeglimin in MASLD with type 2 diabetes: a multicenter study (EASL 2025) - "Imeglimine may be a novel treatment for T2DM complicated by MASLD."

Clinical • Diabetes • Dyslipidemia • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Imeglimin Inhibits Macrophage Foam Cell Formation and Atherosclerosis in Streptozotocin-Induced Diabetic ApoE-Deficient Mice. (PubMed, Cells) - "In diabetic ApoE-/- mice, imeglimin reduced the atherosclerotic plaque area, decreased fasting glucose and LDL cholesterol levels, and upregulated ABCG1 expression in the liver and aorta. These findings suggest that imeglimin may have a preventive effect on foam cell formation and a therapeutic role in atherosclerosis progression in diabetic conditions."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus • ABCG1 • AMPK • APOE • CD36 • SCARB1

The Combination of PPARα Agonist GW7647 and Imeglimin Has Potent Effects on High-Glucose-Induced Cellular Biological Responses in Human Retinal Pigment Epithelium Cells. (PubMed, Bioengineering (Basel)) - "The collective results suggest that Ime in combination with GW has synergetic effects on high-glucose-induced cellular biological changes in ARPE19 cells."

Journal • Diabetes • Diabetic Retinopathy • Retinal Disorders • PPARA

Benefits and disadvantages of combination therapy with imeglimin and metformin in patients with type 2 diabetes. (PubMed, Expert Opin Pharmacother) - "Adding imeglimin to metformin therapy demonstratedfavorable reductions in HbA1c, body weight, and FIB-4 in patients with type 2diabetes, although it was associated with the incidence of gastrointestinalAEs. UMIN000055241."

Journal • Diabetes • Fibrosis • Gastrointestinal Disorder • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and safety of imeglimin add-on to DPP-4 inhibitor therapy in Japanese patients with type 2 diabetes mellitus: An interim analysis of the randomised, double-blind FAMILIAR trial. (PubMed, Diabetes Obes Metab) - "Imeglimin represents a potential new treatment option for patients with T2DM and inadequate glycaemic control with DPP-4 inhibitors, including those aged ≥65 years."

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

Poxel Reports Revenue for the Full Year 2024 and Provides an Update on its Financial Position and Outlook (Poxel Press Release) - "For the quarter ending December 2024, TWYMEEG gross sales in Japan increased by 17% to JPY 2.1 billion (EUR 13 million) over the prior quarter sales of JPY 1.8 billion (EUR 11.2 million) as reported by Sumitomo Pharma. As announced on January 20, 2025, TWYMEEG achieved JPY 5 billion (EUR 30.6 million) net sales in Japan in Sumitomo Pharma’s fiscal year 2024, making Poxel eligible for royalties equalling 10% of all TWYMEEG net sales for 2024 and a sales-based payment of JPY 500 million (EUR 3.1 million)....Sumitomo Pharma is conducting discussions with the regulatory authorities in Japan for revising TWYMEEG package insert for patients with renal impairment. Outcome is expected in the first half of 2025."

Japanese regulatory • Sales • Renal Disease • Type 2 Diabetes Mellitus

High-Glucose-Induced Metabolic and Redox Alterations Are Distinctly Modulated by Various Antidiabetic Agents and Interventions Against FABP5/7, MITF and ANGPTL4 in Melanoma A375 Cells. (PubMed, Int J Mol Sci) - "The anti-diabetic agents metformin (Met) and imeglimin (Ime), inhibitors of fatty acid-binding proteins 5/7 (MF6) and microphthalmia-associated transcription factor (MITF) (ML329), and siRNA-mediated knockdown of angiopoietin-like protein 4 (ANGPTL4), which affect mitochondrial respiration, ROS production, and related gene expression, were tested in A375 (MM cell line) cells cultured in low (5.5 mM) and high glucose (50 mM) conditions. Gene expression related to mitochondrial respiration and the pathogenesis of MM was significantly modulated by different glucose conditions, antidiabetic agents, MF6, and ML329. These findings suggest that glucose-dependent changes in cellular metabolism and redox status are differently modulated by antidiabetic agents, inhibition of fatty acid-binding proteins or MITF, and ANGPTL4 knockdown in A375 cells."

Journal • Diabetes • Melanoma • Oncology • Ophthalmology • Solid Tumor • FABP5 • MITF

A Multicenter, Retrospective Study to Evaluate the Effectiveness and Safety of Imeglimin in Patients with Type 2 Diabetes Mellitus in a Real-World Clinical Setting (INDI-TIMES Study). (PubMed, Diabetes Ther) - "Imeglimin shows promise as an effective and well-tolerated option for managing T2DM in the Indian population. Also, secondary impacts of imeglimin, such as improvements in the lipid profile, hepatic function, blood pressure, and weight loss, warrant further clinical exploration."

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

Two Concerns and A Single Solution in Managing Type 2 Diabetes: A Narrative Review on Imeglimin. (PubMed, J Assoc Physicians India) - "The Trials of Imeglimin for Efficacy and Safety (TIMES) program, consisting of multiple clinical trials, has substantiated the efficacy and safety of imeglimin, illustrating significant glycated hemoglobin (HbA1c) reductions and favorable safety profiles. This review synthesizes evidence from these trials, providing a comprehensive overview of imeglimin as a novel monotherapy and its compatibility in combination therapies, heralding a novel approach to T2D treatment that targets the disease's mitochondrial roots."

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

Poxel Announces the Grant of Patent in China Protecting the Use of Imeglimin for Type-2 Diabetic Patients with Renal Impairment (Businesswire) - "POXEL SA...announced that China's National Intellectual Property Administration ('CNIPA') has granted Poxel patent ZL201980015603.X for Imeglimin, a first-in-class drug targeting mitochondrial dysfunction and marketed in Japan for the treatment of type-2 diabetes. This new patent protects the use of Imeglimin for type-2 diabetic patients with moderate to severe renal impairment until 2039. The granting of the patent further supports ongoing discussions initiated by Poxel to develop and market Imeglimin in China, following the Company's recovery of the rights to this product in Asian countries other than Japan from Sumitomo Pharma."

Patent • Type 2 Diabetes Mellitus