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Clinical pharmacology of imeglimin for the treatment of type 2 diabetes

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Introduction: With the rising prevalence of type 2 diabetes (T2D), there is a substantial interest in novel, glucose-lowering drugs that may complement existing treatment options. Imeglimin is an oral antidiabetic agent currently in clinical development.Areas covered: This review is based on a literature search using PubMed and Embase including all published manuscripts and presentations concerning imeglimin. Supplementary information was retrieved from the manufacturer's official webpage. Preclinical and clinical data are summarized with a focus on mechanisms of action as well as clinical efficacy and safety in T2D.Expert opinion: Imeglimin's mode of action seems to be improved mitochondrial function in pancreatic beta cells leading to improved insulin secretion and lowering of plasma glucose levels. In clinical trials of up to 24 weeks, imeglimin in doses of 1,000-1,500 mg twice daily conferred modest reductions in glycates hemoglobin A1c of 6-11 mmol/mol (0.5-1.0%) (placebo-adjusted) as a monotherapy and 7 mmol/mol (0.6%) as an add-on therapy to metformin or sitagliptin in patients with T2D. Reported adverse effects were mainly gastrointestinal discomfort. The position of imeglimin among other pharmacotherapies in the treatment of T2D will be determined based on future studies more clearly outlining the safety and long-term cardiovascular effects.Abbreviations: AUC: area under the curve; BID: twice daily; DPP-4: dipeptidyl peptidase 4; GLP-1R: glucagon-like peptide-1 receptor; HbA1c: glycated hemoglobin A1c; HFHSD: high-fat high-sucrose diet; OAD: oral antidiabetic; OD: once daily; OGTT: oral glucose tolerance test; PPAR-γ: peroxisome proliferator-activated receptor gamma; PTP: permeability transition pore; SGLT-2: sodium-glucose transport protein 2; STZ: streptozotocin; T2D: type 2 diabetes.

Original languageEnglish
JournalExpert Opinion on Pharmacotherapy
Volume21
Issue number8
Pages (from-to)871-882
Number of pages12
ISSN1465-6566
DOIs
Publication statusPublished - 23 May 2020

    Research areas

  • Imeglimin, oral antidiabetic (OAD), tetrahydrotriazine, type 2 diabees (T2D), Diabetes Mellitus, Type 2/blood, Administration, Oral, Humans, Triazines/administration & dosage, Hypoglycemic Agents/administration & dosage, Blood Glucose/analysis, Insulin-Secreting Cells/drug effects, Insulin/metabolism, Glycated Hemoglobin A/metabolism, Drug Therapy, Combination

ID: 59467655