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https://www.readbyqxmd.com/read/27921428/-promising-molecules-for-treatment-of-hyperglycemia-in-patients-with-type-2-diabetes
#1
Milan Kvapil
New antidiabetic drugs are being developed today that expand the range of pharmacological intervention, in particular for patients with type 2 diabetes (imeglimin, semaglutide, dulaglutide, FGF 21 analogue). At the same time innovations take place that "better" the well-proven molecules, they offer new application forms we have no experience of diabetology (osmotic pump for exenatide, faster acting insulin aspart). New properties are brought by just the change of concentration (insulin glargine in a concentration of 300 U/ml), unexpected positive results are also brought by new fixed-ratio combinations of antidiabetics (fixed-ratio combination of insulin degludec and liraglutide, fixed-ratio combination of insulin glargine and lixisenatide)...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27551496/imeglimin-prevents-human-endothelial-cell-death-by-inhibiting-mitochondrial-permeability-transition-without-inhibiting-mitochondrial-respiration
#2
D Detaille, G Vial, A-L Borel, C Cottet-Rouselle, S Hallakou-Bozec, S Bolze, P Fouqueray, E Fontaine
Imeglimin is the first in a new class of oral glucose-lowering agents, having recently completed its phase 2b trial. As Imeglimin did show a full prevention of β-cell apoptosis, and since angiopathy represents a major complication of diabetes, we studied Imeglimin protective effects on hyperglycemia-induced death of human endothelial cells (HMEC-1). These cells were incubated in several oxidative stress environments (exposure to high glucose and oxidizing agent tert-butylhydroperoxide) which led to mitochondrial permeability transition pore (PTP) opening, cytochrome c release and cell death...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27406738/imeglimin-lowers-glucose-primarily-by-amplifying-glucose-stimulated-insulin-secretion-in-high-fat-fed-rodents
#3
Rachel J Perry, Rebecca L Cardone, Max C Petersen, Dongyan Zhang, Pascale Fouqueray, Sophie Hallakou-Bozec, Sébastien Bolze, Gerald I Shulman, Kitt Falk Petersen, Richard G Kibbey
Imeglimin is a promising new oral antihyperglycemic agent that has been studied in clinical trials as a possible monotherapy or add-on therapy to lower fasting plasma glucose and improve hemoglobin A1c (1-3, 9). Imeglimin was shown to improve both fasting and postprandial glycemia and to increase insulin secretion in response to glucose during a hyperglycemic clamp after 1-wk of treatment in type 2 diabetic patients. However, whether the β-cell stimulatory effect of imeglimin is solely or partially responsible for its effects on glycemia remains to be fully confirmed...
August 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/26881467/investigational-insulin-secretagogues-for-type-2-diabetes
#4
André J Scheen
INTRODUCTION: Insulin secretory defects are a key feature in the pathophysiology of type 2 diabetes (T2D). Classical insulin-secreting agents such as sulfonlyureas stimulate insulin secretion independent of glucose and cause hypoglycemia. Despite the advantages offered by incretin-based therapies, there is still a medical need for developing new insulin secretagogues for treating T2D. AREA COVERED: This article discusses: the new advances in the field of incretin-based therapies, glucokinase (GK) activators, free fatty acid receptor (FFAR) or G protein-coupled receptor (GPR) agonists (GPR40, GPR119, GPR120), imeglimin and some other insulin secretagogues with diverse mechanisms of action still in preclinical development...
2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/26254210/imeglimin-a-potential-new-multi-target-drug-for-type-2-diabetes
#5
Valerie Vuylsteke, Lisa M Chastain, Geeta A Maggu, Crystal Brown
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...
September 2015: Drugs in R&D
https://www.readbyqxmd.com/read/25694060/imeglimin-increases-glucose-dependent-insulin-secretion-and-improves-%C3%AE-cell-function-in-patients-with-type-2-diabetes
#6
RANDOMIZED CONTROLLED TRIAL
G Pacini, A Mari, P Fouqueray, S Bolze, M Roden
AIMS: To assess the glucose-stimulated insulin secretion effect of imeglimin in patients with type 2 diabetes. METHODS: We conducted a double-blind, randomized, placebo-controlled study in 33 patients with type 2 diabetes [glycated haemoglobin 6.8 ± 0.1% (51 mmol/mol)], who were drug-naïve or withdrawn from their previous metformin monotherapy for 2 weeks and received imeglimin 1500 mg twice daily or placebo for 1 week. Glucose-stimulated insulin secretion was assessed using a hyperglycaemic clamp...
June 2015: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/25552598/imeglimin-normalizes-glucose-tolerance-and-insulin-sensitivity-and-improves-mitochondrial-function-in-liver-of-a-high-fat-high-sucrose-diet-mice-model
#7
Guillaume Vial, Marie-Agnès Chauvin, Nadia Bendridi, Annie Durand, Emmanuelle Meugnier, Anne-Marie Madec, Nathalie Bernoud-Hubac, Jean-Paul Pais de Barros, Éric Fontaine, Cécile Acquaviva, Sophie Hallakou-Bozec, Sébastien Bolze, Hubert Vidal, Jennifer Rieusset
Imeglimin is the first in a new class of oral glucose-lowering agents currently in phase 2b development. Although imeglimin improves insulin sensitivity in humans, the molecular mechanisms are unknown. This study used a model of 16-week high-fat, high-sucrose diet (HFHSD) mice to characterize its antidiabetic effects. Six-week imeglimin treatment significantly decreased glycemia, restored normal glucose tolerance, and improved insulin sensitivity without modifying organs, body weights, and food intake. This was associated with an increase in insulin-stimulated protein kinase B phosphorylation in the liver and muscle...
June 2015: Diabetes
https://www.readbyqxmd.com/read/24722500/the-efficacy-and-safety-of-imeglimin-as-add-on-therapy-in-patients-with-type-2-diabetes-inadequately-controlled-with-sitagliptin-monotherapy
#8
RANDOMIZED CONTROLLED TRIAL
Pascale Fouqueray, Valdis Pirags, Michaela Diamant, Guntram Schernthaner, Harold E Lebovitz, Silvio E Inzucchi, Clifford J Bailey
OBJECTIVE: This 12-week study assessed the efficacy and tolerability of imeglimin as add-on therapy to the dipeptidyl peptidase-4 inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled with sitagliptin monotherapy. RESEARCH DESIGN AND METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group study, imeglimin (1,500 mg b.i.d.) or placebo was added to sitagliptin (100 mg q.d.) over 12 weeks in 170 patients with type 2 diabetes (mean age 56...
July 2014: Diabetes Care
https://www.readbyqxmd.com/read/23160726/the-efficacy-and-safety-of-imeglimin-as-add-on-therapy-in-patients-with-type-2-diabetes-inadequately-controlled-with-metformin-monotherapy
#9
RANDOMIZED CONTROLLED TRIAL
Pascale Fouqueray, Valdis Pirags, Silvio E Inzucchi, Clifford J Bailey, Guntram Schernthaner, Michaela Diamant, Harold E Lebovitz
OBJECTIVE: A 12-week study assessed the efficacy and safety of a new oral antidiabetic agent, imeglimin, as add-on therapy in type 2 diabetes patients inadequately controlled with metformin alone. RESEARCH DESIGN AND METHODS: A total of 156 patients were randomized 1:1 to receive imeglimin (1,500 mg twice a day) or placebo added to a stable dose of metformin (1,500-2,000 mg/day). Change in A1C from baseline was the primary efficacy outcome; secondary outcomes included fasting plasma glucose (FPG) and proinsulin/insulin ratio...
March 2013: Diabetes Care
https://www.readbyqxmd.com/read/22519919/imeglimin-a-novel-glimin-oral-antidiabetic-exhibits-a-good-efficacy-and-safety-profile-in-type-2-diabetic-patients
#10
RANDOMIZED CONTROLLED TRIAL
V Pirags, H Lebovitz, P Fouqueray
AIMS: Imeglimin is the first in a new tetrahydrotriazine-containing class of oral antidiabetic agents, the glimins. It has been shown to act on the liver, muscle and pancreatic β-cells to uniquely target the key defects of type 2 diabetes. Two studies were performed to compare the safety and efficacy of imeglimin with metformin and placebo on glycaemic control in type 2 diabetes patients. METHODS: In a 4-week phase IIa, three-arm parallel group study, patients were randomized to imeglimin 2000 mg once daily (od), imeglimin 1000 mg twice daily (bid) or metformin 850 mg bid and responses to an oral glucose tolerance test (OGTT) were measured...
September 2012: Diabetes, Obesity & Metabolism
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