Evaluating Imeglimin as a Novel Therapeutic Action Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

INTRODUCTION/OBJECTIVE: Imeglimin is the first agent of the novel glimin class that targets mitochondrial dysfunction, a key pathophysiological mechanism underlying type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of imeglimin in patients with T2DM. METHODS: A systematic literature search was conducted in PubMed, Scopus, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from database inception to December 2025. Randomized controlled trials (RCTs) and prospective observational studies evaluating imeglimin as monotherapy or combination therapy were included. Risk of bias was assessed using the Cochrane RoB 2.0 and ROBINS-I tools. Continuous outcomes were pooled as mean differences (MDs) and dichotomous outcomes as risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Twenty-four studies were included in the qualitative synthesis, comprising 13 experimental studies and 11 observational studies. Thirteen RCTs involving 1,925 participants were eligible for quantitative meta-analysis. Imeglimin significantly reduced glycated haemoglobin (HbA1c) compared with control therapy (MD -0.21%; 95% CI: -0.25 to -0.17), although substantial heterogeneity was observed (I2 = 96.1%). Fasting plasma glucose (FPG) was also significantly reduced (MD -0.97 mmol/L; 95% CI: -1.08 to -0.86; I2 = 92.3%). No statistically significant increase in serious adverse events was identified. Gastrointestinal adverse events were primarily dose-related and generally mild. Although the pooled analysis showed an increased risk of hypoglycaemia, subgroup analyses were limited by low event rates and wide confidence intervals. DISCUSSION: Imeglimin demonstrated consistent improvements in glycaemic control, particularly when used in combination with other antidiabetic therapies. Variations in study design, treatment duration, baseline glycaemic status, and comparator regimens likely contributed to the observed heterogeneity. CONCLUSION: Imeglimin is an effective glucose-lowering therapy with an acceptable safety profile in patients with T2DM. Optimal efficacy appears to be achieved at doses of 1000-1500 mg twice daily, particularly as add-on therapy. Further large-scale, long-term studies are required to evaluate cardiovascular and renal outcomes and establish its role in routine clinical practice.