Real-World Effectiveness and Safety of Imeglimin: A Single-Center Retrospective Cohort Study in Japan

Taro Fujisawa^1,2Takehiro Kato^1*Kazuhisa Takami²Shinya Fukuda²Risako Imai²Tomoya Kawashima²Ryosuke Horita²Katsuhisa Sakai²Akiko Yamada²Shin Tsunekawa^1,3Daisuke Yabe^1,3,4

• ¹Department of Diabetes, Endocrinology and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu, Japan
• ²Department of Endocrinology and Metabolism/Diabetes Center, Central Japan International Medical Center, Minokamo, Japan
• ³Center for One Medicine Innovative Translational Research, Gifu University Institute for Advanced Studies, Gifu, Japan
• ⁴Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan

Aims/Introduction: This study aimed to evaluate the real-world effectiveness and safety of imeglimin in individuals with type 2 diabetes. Materials and Methods: We retrospectively reviewed 79 individuals (52 men, 27 women) with type 2 diabetes who newly initiated imeglimin (1,000 mg twice daily) and were followed for 12 months at the Central Japan International Medical Center between September 2022 and December 2023. Individuals were stratified by age (<65, 65–74, ≥75 years) and by the presence or absence of biguanide dose reduction at imeglimin initiation. The primary endpoint was the change in HbA1c from baseline to 12 months. Secondary endpoints included the achievement rate of glycemic targets, incidence of adverse events, and changes in body weight, blood pressure, liver and renal function, lipid profile, and uric acid. Results: HbA1c significantly decreased one month after initiation and the improvement was sustained through 12 months (mean change from baseline -0.8±1.2%). Effectiveness and safety did not differ significantly among age groups. Gastrointestinal symptoms were the most common adverse events (21.5%), with no age-related differences. HbA1c reduction was greater in individuals without biguanide dose reduction compared with those with dose reduction (–1.5±1.7% vs – 0.5±0.7%, p=0.019), although adverse event frequency was comparable. Importantly, gastrointestinal disturbances were more frequent when imeglimin was combined with metformin ≥1,000 mg/day (p=0.032). Significant reductions were also observed in body weight, triglycerides, and liver enzymes at 12 months. Conclusions: Imeglimin demonstrated sustained glycemic effectiveness and favorable tolerability in real-world practice, including among elderly individuals with type 2 diabetes. These findings suggest imeglimin as a valuable therapeutic option for older adults with type 2 diabetes. Caution is warranted when co-administered with high-dose metformin, whereas combination with <1,000 mg/day appears relatively safe.