G Pacini1, A Mari1, P Fouqueray2, S Bolze2, M Roden3,4,5. 1. Metabolic (Modeling) Unit, Institute of Biomedical Engineering, Padova, Italy. 2. Poxel SA, Lyon, France. 3. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Düsseldorf, Germany. 4. Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. 5. German Center for Diabetes Research, Düsseldorf, Germany.
Abstract
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study in 33 patients with type 2 diabetes [glycated haemoglobin 6.8 ± 0.1% (51 mmol/mol)], who were drug-naïve or withdrawn from their previous metformin monotherapy for 2 weeks and received imeglimin 1500 mg twice daily or placebo for 1 week.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. The primary endpoint was insulin secretion as defined by total insulin response [incremental area under the curve (iAUC)0-45 min ] and insulin secretion rate (ISR) calculated from C-peptide deconvolution. β-cell glucose sensitivity at steady state (second phase: 25-45 min), hepatic insulin extraction and insulin clearance were also calculated. RESULTS:Imeglimin treatment for 7 days raised the insulin secretory response to glucose by +112% (iAUC0-45 , p = 0.035), first-phase ISR by +110% (p = 0.034) and second-phase ISR by +29% (p = 0.031). Imeglimin improved β-cell glucose sensitivity by +36% (p = 0.034) and tended to decrease hepatic insulin extraction (-13%; p = 0.056). Imeglimin did not affect glucagon secretion. CONCLUSIONS: In patients with type 2 diabetes, imeglimin improves β-cell function, which may contribute to the glucose-lowering effect observed with imeglimin in clinical trials.
RCT Entities:
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study in 33 patients with type 2 diabetes [glycated haemoglobin 6.8 ± 0.1% (51 mmol/mol)], who were drug-naïve or withdrawn from their previous metformin monotherapy for 2 weeks and received imeglimin 1500 mg twice daily or placebo for 1 week.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. The primary endpoint was insulin secretion as defined by total insulin response [incremental area under the curve (iAUC)0-45 min ] and insulin secretion rate (ISR) calculated from C-peptide deconvolution. β-cell glucose sensitivity at steady state (second phase: 25-45 min), hepatic insulin extraction and insulin clearance were also calculated. RESULTS:Imeglimin treatment for 7 days raised the insulin secretory response to glucose by +112% (iAUC0-45 , p = 0.035), first-phase ISR by +110% (p = 0.034) and second-phase ISR by +29% (p = 0.031). Imeglimin improved β-cell glucose sensitivity by +36% (p = 0.034) and tended to decrease hepatic insulin extraction (-13%; p = 0.056). Imeglimin did not affect glucagon secretion. CONCLUSIONS: In patients with type 2 diabetes, imeglimin improves β-cell function, which may contribute to the glucose-lowering effect observed with imeglimin in clinical trials.
Authors: 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 Journal: Am J Physiol Endocrinol Metab Date: 2016-07-12 Impact factor: 4.310
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