Imeglimin as an effective therapeutic approach in management of type 2 diabetes mellitus: an umbrella review and systematic review, meta-regression and meta-analysis.

BACKGROUND: Imeglimin as a novel antidiabetic agent has emerged promising effects compared to previously established treatments. This updated systematic review and meta-analysis and umbrella review evaluated the efficacy and safety of Imeglimin in managing Type 2 Diabetes Mellitus (T2DM). METHODS: A systematic search of PubMed, Scopus, Web of Science, Embase, and Cochrane Central was conducted up to June 2025. Randomized controlled trials (RCTs) with at least 12 weeks of follow-up, involving adult T2DM patients, were included. Data were independently extracted by two reviewers, and any discrepancies were resolved by a third investigator. Outcomes were pooled using random-effects or fixed-effects models based on heterogeneity. The quality of the included trials was assessed using the Cochrane Risk of Bias 2.0 tool. Also, the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to evaluate the certainty of evidence. RESULTS: Twelve RCTs evaluating the effect of imeglimin on metabolic factors were included. Imeglimin significantly reduced fasting plasma glucose (FPG) (SMD: -0.51; 95% CI: -0.72, -0.29, P < 0.001; I2 = 75.27%, P-heterogeneity < 0.001) and HbA1c (SMD: -0.45; 95% CI: -0.86, -0.05, P = 0.031; I2 = 94.10%, P-heterogeneity < 0.001). Also, it improved homeostasis model assessment of β-cell function (HOMA-β) (SMD: 0.59; 95% CI: 0.18, 1.01, P = 0.020; I2 = 59.30%, P-heterogeneity = 0.06). Whereas, imeglimin failed to affect insulin, level, HOMA-IR, and c-peptide level, significantly (P > 0.05). However, its unfavorable effect was shown in term of LDL (SMD: 0.32; 95% CI: 0.11, 0.53, P = 0.017; I2 = 0.0%, P-heterogeneity = 0.68). CONCLUSION: Imeglimin has demonstrated efficacy and a favorable safety profile in the management of T2DM, particularly regarding glycemic control and lipid profile. Further large-scale trials across diverse populations are warranted to confirm these outcomes.