Efficacy and safety of imeglimin in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized clinical trials

Imeglimin is a novel tetrahydrotriazine-containing drug suggested as a safe drug for glycemic management in patients with type 2 diabetes mellitus (T2DM). We aimed to 1) evaluate the efficacy of imeglimin on glycemic control and insulin resistance improvement measured by homeostatic model assessment of insulin resistance (HOMA-IR). 2) assess whether the novel drug improves lipid parameters in diabetic patients. 3) compare between different doses regarding safety.We searched PubMed, Cochrane Library, Scopus, Web of Science, Google Scholar, and Wiley through April 25, 2021, for relevant randomized controlled trials comparing different doses of imeglimin supplied as a monotherapy or as add-on therapy versus placebo for adult patients with type 2 diabetes mellitus. Data on glycemic and lipid parameters and adverse events were extracted and pooled in random-effect models using Review Manager version 5.3.Eight studies comprising 1555 patients with T2DM were included in this study. The overall effect estimate of the meta-analysis showed that the imeglimin group was superior to the control group concerning glycated hemoglobin and fasting plasma glucose (P < 0.00001). However, it did not affect HOMA-IR or lipid parameters, including triglyceride, LDL-C, and HDL-C (all p > 0.05). Regarding safety profile, imeglimin was safe and tolerable with no treatment-emergent or serious adverse events.Imeglimin safely improved glycemic control by reducing HbA1c and FPG. However, no beneficial effects regarding insulin resistance measured by HOMA-IR or lipid parameters were observed. Further high-quality RCTs with high dose imeglimin are encouraged to ensure HOMA-IR and lipid parameters results.