Efficacy and safety of imeglimin, a novel oral agent in the management of type 2 diabetes mellitus: a systematic review and meta-analysis.

This systematic review and meta-analysis evaluated the efficacy and safety of Imeglimin in managing type-2 diabetes mellitus (T2DM). A systematic search of PubMed, Embase, and Cochrane Central was conducted up to March 26, 2025. Randomized controlled trials (RCTs) in T2DM subjects with at least two treatment arms were included in the qualitative analysis. Imeglimin, as monotherapy or in combination with other anti-diabetic agents, was compared to placebo or other treatments. Data were independently extracted by three authors, with discrepancies resolved by two other authors. Outcomes were pooled using random-effects or fixed-effects models based on heterogeneity. Thirteen RCTs and nine observational studies were included in the quantitative and qualitative analyses, respectively. Imeglimin significantly reduced glycated haemoglobin/haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG), with greater efficacy at higher doses and in combination therapy. It improved β-cell function (HOMA-β) without significant effects on insulin resistance (HOMA-IR). No major adverse events were reported. However, the studies were limited to Japanese (Asian) and Caucasian populations, affecting generalizability. Significant heterogeneity amongst studies for some outcomes further indicates the need for comprehensive clinical trials with greater sample sizes and uniform dose ranges and follow-up periods. Imeglimin is an effective and safe option for T2DM, particularly for improving glycemic control and β-cell function. Further studies in diverse populations are needed to confirm these findings. Trial Registration: PROSPERO (CRD42024564036).