Imeglimin: A Potential New Multi-Target Drug for Type 2 Diabetes

Abstract

Imeglimin is a novel agent currently in development to treat type 2 diabetes. Laboratory studies have demonstrated that it has the potential to impact the three main pathophysiologic components of type 2 diabetes: impaired glucose uptake by muscle tissue, excess hepatic gluconeogenesis, and increased beta-cell apoptosis. Preliminary human studies that have been published within the last 2 years demonstrate that imeglimin improves hemoglobin A1c and fasting plasma glucose similarly when compared with metformin and with sitagliptin. There has also been a low incidence of adverse effects, especially hypoglycemia, reported in these early human studies. Currently, imeglimin is lacking long-term evidence to demonstrate any effects on its cardiovascular safety, and data on morbidity and mortality, though some studies are currently in progress. There is great potential for imeglimin, if FDA approved, to play a significant role in the type 2 diabetes management algorithm.

A review of phenformin, metformin, and imeglimin

“…Imeglimin is an emerging as a novel glucose‐reducing agent. In diabetic rats, plasma glucose was reduced with imeglimin treatment (25, 50, and 100 mg/kg) in a similar manner to metformin (50 mg/kg; Fouqueray et al, ) and shown to target all three of the contributing physiologic defects in type 2 diabetes (Fouqueray et al, ; Vuylsteke, Chastain, Maggu, & Brown, ; Table ). Imeglimin (200 mg/kg, b.i.d.…”

Molecular Mechanisms by Which Imeglimin Improves Glucose Homeostasis

“…Imeglimin, with the chemical name of (6R)-(+)-4-dimethylamino-2-imino-6-methyl-1,2,5,6-tetrahydro-1,3,5-triazine hydrochloride, is a new promising antidiabetic medication which has demonstrated antihyperglycemic effects in various studies [8,11]. It is an inhibitor of the oxidative-phosphorylation process taking place inside the mitochondria of aerobic cells and thereby can exert potent metabolic effects in eukaryotic cells [12].…”

“…Therefore, it has potential advantages to other oral hypoglycemic agents, which target only one or two defects and not all the three defects, namely, increased glycogenesis in the liver, impaired insulin secretion from the pancreas, and insulin resistance in muscles. Thereby, imeglimin is one of the potentially promising medications for managing patients with T2DM, if approved [8] (Table 1).…”

“…Many pharmacological agents have been developed to improve hyperglycemia and prevent complications associated with diabetes [7]. Imeglimin is a novel and promising antihyperglycemic agent but has not been approved yet for managing patients with diabetes [8,9]. All of the pharmacological properties of ime-glimin and the mechanisms behind its therapeutic effect have not been fully elucidated [8,10].…”

“…Imeglimin is a novel and promising antihyperglycemic agent but has not been approved yet for managing patients with diabetes [8,9]. All of the pharmacological properties of ime-glimin and the mechanisms behind its therapeutic effect have not been fully elucidated [8,10]. We searched for related articles using keywords of imeglimin and diabetes mellitus in various databases such as PubMed, Medline, and Scopus which evaluated the possible mechanism of action of imeglimin in diabetes.…”