Imeglimin, a novel drug for type 2 diabetes (T2D), is under investigation in the INFINITY study to evaluate its impact on glycemic control markers and erythrocytes. This single-center, single-arm, open-label, prospective study aims to determine if the standard HbA1c measurement accurately reflects imeglimin's glucose-lowering effects, given its potential influence on erythrocyte lifespan and function.
The study, registered in the Japan Registry of Clinical Trials (jRCTs031220489), involves 30 patients with T2D and inadequate glycemic control. Participants will receive 2,000 mg of imeglimin daily for six months. Researchers will compare HbA1c levels with glycoalbumin (GA) and 1,5-anhydroglucitol (1,5-AG) to assess the divergence in glycemic reduction rates. The trial will also explore imeglimin's effects on erythrocytes, including lifespan, deformability, and hemoglobin concentration.
Study Design and Objectives
The INFINITY study seeks to confirm the divergence between HbA1c and the glycemic reduction rate of GA and 1,5-AG in T2D patients treated with imeglimin. Continuous glucose monitoring will be used to assess glycemic variability and its relationship with changes in HbA1c, GA, and 1,5-AG. The study will also investigate whether imeglimin's effects on erythrocyte lifespan contribute to discrepancies in HbA1c measurements.
Inclusion and Exclusion Criteria
Eligible participants include T2D patients aged 20 years or older with an HbA1c between 6.5% and 8.5%, treated with diet and exercise alone or in combination with α-glucosidase inhibitors (excluding acarbose) or metformin. Exclusion criteria include the use of other diabetes medications, anemia, hypoalbuminemia, thyroid impairment, liver cirrhosis, moderate to severe renal impairment, and the use of antiplatelet or antithrombotic drugs.
Outcome Measures
The primary outcome is the change in hemoglobin concentration between baseline and six months after imeglimin treatment. Secondary outcomes include changes in erythrocyte lifespan, deformability, red blood cell count, HbA1c, GA, 1,5-AG, and various glycemic variability metrics. Safety outcomes include the incidence of adverse events, changes in liver function markers, lipid markers, blood pressure, pulse rate, and body weight.
Potential Impact on Peripheral Arterial Disease
If imeglimin improves erythrocyte deformability, it could potentially improve peripheral arterial occlusive disease, a chronic complication of T2D. The study will evaluate the toe-brachial pressure index, a measure of this effect.
Imeglimin's Mechanism and Erythrocyte Function
Imeglimin's mechanism of action involves improving mitochondrial function and reducing oxidative stress in key organs involved in T2D pathophysiology. It may also influence erythrocyte function by increasing erythrocyte NAD+ levels, potentially affecting erythrocyte lifespan and deformability.
Trial Status and Ethics
The study protocol was approved by the Certified Clinical Research Review Board of Toho University. Enrollment began in February 2023 and is expected to be completed by December 2023. The study is being conducted in accordance with the ethical principles of the Declaration of Helsinki and the Clinical Research Act.
