Abstract
Imeglimin is the first of the “glimins,” a new class of drugs developed for the treatment of type 2 diabetes mellitus (T2DM). This review highlights its mechanism of action and its context in the field of T2DM treatment. Preclinical data in multiple rodent models have detailed significant effects on mitochondria, particularly improved mitochondrial bioenergetics. This includes changes favoring complex II and complex III metabolism, a mechanism potentially promoting increased fatty acid oxidation, leading to the decrease in hepatic lipid accumulation observed in these mice. Imeglimin was also shown to increase muscle glucose uptake and decrease hepatic glucose production, both in vitro and in vivo. Though studies have also shown imeglimin to significantly improve insulin secretion and decrease β-cell death, whether its physiologic effects are purely insulin dependent remains unclear. Early preclinical studies have shown evidence for improvements in cardiac and renal function in rats with metabolic syndrome, effects not conferred by most currently available T2DM drugs. Clinical studies of imeglimin in humans have shown increased insulin secretion, along with decreased fasting plasma glucose and glycated hemoglobin. Its observed efficacy was comparable to that of currently available agents metformin and sitagliptin and was increased when given in combination with either agent. When considered alongside its benign safety profile reported in patients with chronic kidney disease, imeglimin shows true promise to provide a novel mechanism for T2DM treatment, with potential application in a larger, more comprehensive patient population.
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R.J.P. received speaker honoraria from the Japan Diabetes Society in 2018 and 2020 and has received investigator-initiated research support from AstraZeneca to explore the mechanism by which SGLT2 inhibitors may cause ketoacidosis in rodents.
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Konkwo, C., Perry, R.J. Imeglimin: Current Development and Future Potential in Type 2 Diabetes. Drugs 81, 185–190 (2021). https://doi.org/10.1007/s40265-020-01434-5
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DOI: https://doi.org/10.1007/s40265-020-01434-5