Real-World Study Shows Sustained Glycaemic Benefit and Acceptable Safety of Imeglimin in Type 2 Diabetes

The findings were published in Frontiers in Clinical Diabetes and Healthcare in December 2025

Imeglimin addresses the distinct pathophysiology of T2D by enhancing glucose-dependent insulin release and improving hepatic metabolism through mitochondrial modulation. While the Trials of Imeglimin for Efficacy and Safety (TIMES 1–3) confirmed its initial clinical profile, the authors note a significant evidence gap regarding the medication's performance in routine practice, particularly for the growing elderly population and its safety when combined with biguanide (BG) therapies. To address this, Taro Fujisawa, Takehiro Kato, and colleagues of the Central Japan International Medical Center aimed to evaluate the 12-month real-world effectiveness and safety of imeglimin, stratified by age and concurrent BG dosing.

The investigators conducted a single-centre, retrospective observational study involving 79 individuals with T2D (52 men and 27 women) who newly initiated imeglimin at a dose of 1,000 mg twice daily between September 2022 and December 2023. Participants were stratified by age (<65, 65–74, and ≥75 years) and by the presence or absence of biguanide dose reduction at the time of imeglimin initiation. The primary endpoint was change in HbA1c from baseline to 12 months, while secondary endpoints included adverse events and changes in body weight, blood pressure, lipid profile, liver and renal function, and uric acid levels.

Key Clinical Findings of the Study:

• Sustained Glycemic Efficacy: The study reveals that imeglimin resulted in a significant and durable mean reduction in HbA1c of 0.8 ± 1.2% over a 12-month period, with clinical improvements observed as early as one month after initiation.
• High Success in Older Populations: Imeglimin proved exceptionally effective in the elderly, with T2D patients aged 75 years and older achieving an 86% glycemic target success rate without significant differences in safety compared to younger cohorts.
• Metformin Dosing and GI Safety: While GI disturbances were the most common adverse event at 21.5%, clinicians should note that the risk was significantly higher when imeglimin was co-administered with metformin at doses of 1,000 mg/day or more.
• Optimizing Concurrent BG Therapy: Patients who maintained their full BG dosage experienced a significantly greater decline in HbA1c (−1.5 ± 1.7%) compared to those who reduced their dose (−0.5 ± 0.7%), suggesting that maintaining BG therapy maximizes the drug's additive effects.
• Extrapancreatic Metabolic Benefits: Beyond glucose regulation, 12 months of therapy led to significant clinical improvements in BW, triglycerides (TG), and liver enzymes, including ALT and AST.

The results suggest imeglimin provides durable T2D control with a 0.8% mean HbA1c reduction and an 86% target success rate in patients 75+, though clinicians must monitor GI risks when it is combined with metformin at 1,000 mg/day or more.

The authors concluded that imeglimin demonstrated sustained glycaemic effectiveness and acceptable tolerability in real-world clinical practice, including among elderly individuals with T2D. They noted that caution may be warranted when imeglimin is co-administered with high-dose metformin, while combination with lower metformin doses appeared relatively safe.

Reference:

Fujisawa T, Kato T, Takami K, et al. Real-world effectiveness and safety of imeglimin: a single-center retrospective cohort study in Japan. Front. Clin. Diabetes Healthc. 2025;6:1694522.