Imeglimin: Current Development and Future Potential in Type 2 Diabetes
- PDF / 673,455 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 95 Downloads / 207 Views
LEADING ARTICLE
Imeglimin: Current Development and Future Potential in Type 2 Diabetes Chigoziri Konkwo1,2 · Rachel J. Perry1,2
© Springer Nature Switzerland AG 2020
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. Key Points Glimins are robust glucose-lowering agents that likely have a multifactorial mechanism of action. The glimin furthest along in preclinical and clinical studies is imeglimin. It has been suggested that imeglimin lowers glucose by increasing insulin secretion, enhancing mitochondrial bioenergetics, increasing muscle glucose uptake, and decreasing hepatic glucose production. In contrast to commonly used hypoglycemic agents, the adverse effect profile of imeglimin is generally benign, including in those with diabetic kidney disease.
* Rachel J. Perry [email protected] 1
Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT, USA
2
1 Introduction Type 2 diabetes mellitus (T2DM) is a disease that has continued to grow in prevalence, with an estimated 463 million people aged 20–79 years living with diabetes worldwide in 2019 and an expected 700 million by 2045 [1]. As a metabolic disorder highlighted by poor glycemic control, secondary to a complex interplay between both insulin resistance in peripheral organs, and decreased β-cell function, effective management and treatment of the co
Data Loading...
