title: Differential effects of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide and metformin on pancreatic β-cell and insulin sensitivity during a standardized test meal in patients with type 2 diabetes.
abstract: This substudy of the AWARD-3 trial evaluated the effects of the once-weekly glucagon-like peptide-1 receptor agonist, dulaglutide, versus metformin on glucose control, pancreatic function and insulin sensitivity, after standardized test meals in patients with type 2 diabetes. Meals were administered at baseline, 26 and 52 weeks to patients randomized to monotherapy with dulaglutide 1.5 mg/week (n = 133), dulaglutide 0.75 mg/week (n = 136), or metformin ≥1500 mg/day (n = 140). Fasting and postprandial serum glucose, insulin, C-peptide and glucagon levels were measured up to 3 h post-meal. β-cell function and insulin sensitivity were assessed using empirical variables and mathematical modelling. At 26 weeks, similar decreases in area under the curve for glucose [AUCglucose (0-3 h)] were observed among all groups. β-cell function [AUCinsulin /AUCglucose (0-3 h)] increased with dulaglutide and was unchanged with metformin (p ≤ 0.005, both doses). Dulaglutide improved insulin secretion rate at 9 mmol/l glucose (p ≤ 0.04, both doses) and β-cell glucose sensitivity (p = 0.004, dulaglutide 1.5 mg). Insulin sensitivity increased more with metformin versus dulaglutide. In conclusion, dulaglutide improves postprandial glycaemic control after a standardized test meal by enhancing β-cell function, while metformin exerts a greater effect on insulin sensitivity.
authors.affiliation: National Research Council, Institute of Neuroscience, Padova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mari
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, Pisa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Del Prato
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Ludvik
authors.affiliation: Eli Lilly and Company, Vienna, Austria.
authors.forename: Z
authors.initials: Z
authors.lastname: Milicevic
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: A
authors.initials: A
authors.lastname: de la Peña
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: L
authors.initials: L
authors.lastname: Shurzinske
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Karanikas
authors.affiliation: Eli Lilly and Company, Neuilly-sur-Seine, France.
authors.forename: V
authors.initials: V
authors.lastname: Pechtner
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005215:Fasting; D005260:Female; D005934:Glucagon / Q000378:metabolism; D004763:Glucagon-Like Peptides / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D019518:Postprandial Period; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016896:Treatment Outcome; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005934:Glucagon; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D007328:Insulin; D008687:Metformin; D011993:Recombinant Fusion Proteins; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C517652:hemoglobin A1c protein, human; C555680:dulaglutide
keywords: GLP-1 receptor agonists; dulaglutide; metformin; type 2 diabetes; β cells