Breakthrough Clinical Results
Poxel SA announced that five presentations on the therapeutic potential of Imeglimin (TWYMEEG®), a first-in-class treatment for type 2 diabetes, will be featured at the 85th Scientific Sessions of the American Diabetes Association (ADA 2025). These presentations, delivered by leading Japanese diabetes experts, will cover various aspects of Imeglimin's efficacy, including its impact on diabetic kidney disease, insulin sensitivity, glycemic control, diabetic neuropathy, and periodontitis. The presentations include data from two clinical trials and three non-clinical studies, further supporting Imeglimin's value as a treatment for type 2 diabetes and its associated conditions. Imeglimin is currently marketed in Japan by Sumitomo Pharma, with Poxel receiving royalties and sales-based payments.
Key Highlights
- Five presentations on Imeglimin's potential will be made at ADA 2025.
- Presentations include data from two clinical trials and three non-clinical studies.
- Imeglimin's potential benefits across various diabetic complications will be discussed.
- The presentations highlight ongoing enthusiasm within the scientific community for Imeglimin.
Incidence and Prevalence
The global prevalence of type 2 diabetes is a significant and growing health concern. Several studies provide estimates, though variations exist due to methodologies and data sources. Here's a summary of some of the latest estimates:
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2021:
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10.5% (536.6 million people) in adults aged 20-79 years. This is projected to rise to 12.2% (783.2 million) by 2045. Prevalence was higher in urban (12.1%) vs. rural (8.3%) areas, and in high-income (11.1%) vs. low-income (5.5%) countries. The largest relative increase in prevalence between 2021 and 2045 is expected in middle-income countries (21.1%).
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1 in 10 adults worldwide had diabetes. The estimated prevalence in adults aged 20-79 years was 537.5 million (10.5%), projected to rise to over 12.8% by 2045.
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Global prevalence of type 1 diabetes was estimated at 8.4 million individuals, with 0.5 million new cases diagnosed. Life expectancy for a 10-year-old diagnosed with type 1 diabetes ranged from 13 years in low-income countries to 65 years in high-income countries.
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2019:
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9.3% (463 million people) globally, rising to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045. Prevalence was higher in urban (10.8%) vs. rural (7.2%) areas, and in high-income (10.4%) vs. low-income countries (4.0%). Half of those living with diabetes were unaware of their condition.
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Global burden showed an increase, with the low-middle socio-demographic index region experiencing the highest rise in age-standardized rates. The global age-standardized incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates were 259.9, 5282.9, 18.5, and 801.5 per 100,000 population, respectively.
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5282.9 per 100,000 globally, with an increase of 49% since 1990. The highest rates were in American Samoa (19,876.8 per 100,000). The burden generally decreased with increasing Socio-demographic Index.
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2017:
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462 million individuals (6.28% of the world's population). This included 4.4% of those aged 15-49 years, 15% of those aged 50-69, and 22% of those aged 70+. The prevalence rate was 6059 cases per 100,000. Over 1 million deaths per year were attributed to diabetes, making it the ninth leading cause of mortality.
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8.8% of the world population, with an anticipated increase to 9.9% by 2045. This translates to 424.9 million people in 2017, projected to rise to 628.6 million by 2045. Prevalence varied by age: around 5% for ages 35-39, 10% for 45-49, 15% for 55-59, and close to 20% for 65-69 years.
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Global incidence, prevalence, death, and DALYs were 22.9 million, 476.0 million, 1.37 million, and 67.9 million, respectively, projected to increase to 26.6 million, 570.9 million, 1.59 million, and 79.3 million by 2025.
These figures highlight the continued rise in type 2 diabetes globally, emphasizing the need for preventive measures and effective management strategies.
Emerging Mechanism of Action
Several key mechanisms of action (MoAs) are emerging for Type 2 diabetes treatment, based on recent PubMed publications:
1. GLP-1 Receptor Agonists (GLP-1 RAs) and Dual/Triple Agonists:
- GLP-1 RAs mimic the incretin hormone GLP-1, augmenting glucose-stimulated insulin secretion, suppressing glucagon secretion, slowing gastric emptying, and promoting weight loss. Semaglutide, available in oral and injectable forms, is a prominent example. Research also explores combining semaglutide with cagrilintide, a long-acting amylin analogue.
- Dual and Triple Agonists: These combine GLP-1 RA activity with other gut hormone actions. Tirzepatide, a GLP-1/GIP receptor agonist, shows high efficacy in glucose lowering and weight loss. Unimolecular dual agonists (GLP-1/glucagon) and triagonists (GLP-1/glucagon/GIP) are also under investigation.
2. SGLT2 Inhibitors:
- These drugs block glucose reabsorption in the kidneys, increasing glucose excretion in urine and lowering blood glucose levels. They also offer benefits in weight loss, blood pressure reduction, and cardiovascular and renal protection. Empagliflozin is a key example, demonstrating slower kidney disease progression and reduced renal events.
3. Multi-receptor Agonists:
- LY3437943, a single peptide agonist for glucagon, GIP, and GLP-1 receptors, is under development. Early-phase studies show promising safety, pharmacokinetics, and pharmacodynamics, with robust glucose and weight reduction.
4. Smart Insulin Preparations:
- These insulins have a glucose-dependent mode of action, aiming to provide more physiological insulin delivery and reduce hypoglycemia risk.
5. Novel Targets and Mechanisms:
- Adiponectin and FGF21: Research explores the potential of these adipokines and hepatokines for glucose lowering.
- Small molecule GLP-1 receptor activators: These offer an alternative to peptide-based GLP-1 RAs.
- Bariatric Surgery and Gut Hormonal Milieu: Bariatric surgery's impact on gut hormones provides a basis for developing multi-receptor agonists.
- Imeglimin: This first-in-class drug targets mitochondrial dysfunction, a key element in T2DM pathogenesis, by rebalancing respiratory chain activity and reducing oxidative stress.
- Berberine: This compound inhibits voltage-gated potassium channels in pancreatic beta cells, promoting glucose-dependent insulin secretion without causing hypoglycemia.
- Tirzepatide: This novel agent has shown substantial weight reduction and a lower risk of progression to type 2 diabetes in individuals with obesity and prediabetes.
Challenges and Future Directions:
- Medication Adherence: Poor adherence remains a major challenge in realizing the full potential of existing therapies.
- Precision Medicine: Research aims to identify subgroups of patients who benefit most from specific treatments, including pharmacogenomic approaches.
- Diabetes Reversal: Bariatric surgery, low-calorie diets, and carbohydrate restriction show promise for T2DM reversal, but require further research and integration into guidelines.
- Emerging Technologies: Advances in continuous glucose monitoring, insulin pumps, and automated insulin delivery systems offer improved disease management.
- Gut Microbiota Modulation: Targeting GM dysbiosis through dietary interventions or fecal microbiota transplantation holds potential for treating obesity and related metabolic disorders.
These MoAs represent the evolving landscape of T2DM treatment, with a focus on improving glycemic control, promoting weight loss, and addressing cardiovascular and renal complications. Ongoing research and clinical trials will further refine these approaches and potentially lead to curative treatments.
Drug used in other indications
Imeglimin, the first in the glimin class of diabetes medications, is primarily being investigated for its efficacy in treating type 2 diabetes mellitus (T2DM). While its unique mechanism of action, targeting mitochondrial dysfunction and improving cellular energy metabolism, holds promise for broader applications, current research and clinical trials predominantly focus on T2DM. Some studies suggest potential benefits in related metabolic conditions, but these are not yet the focus of large-scale clinical trials.
One area of exploration is diabetic complications. Preclinical studies have shown some evidence of improvement in cardiac and renal function in rats with metabolic syndrome. Further research is needed to determine if these effects translate to humans and if imeglimin could be a viable treatment option for these complications.
Additionally, imeglimin's impact on mitochondrial bioenergetics may have implications for other conditions beyond diabetes. However, specific clinical trials for these indications are not yet readily apparent in the provided literature. More research is needed to explore the full therapeutic potential of imeglimin outside of T2DM.
The provided research primarily discusses the use of imeglimin in the context of randomized controlled trials (RCTs) for T2DM. These trials compare imeglimin to placebo, metformin, or other existing antidiabetic agents. The interventions typically involve administering imeglimin as monotherapy or in combination with other medications, with outcomes measured by changes in HbA1c, fasting plasma glucose, and other metabolic parameters. While some preclinical studies utilize animal models, the clinical trials for T2DM primarily employ RCTs as the intervention model.