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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
Author(s) -
Mari A.,
Del Prato S.,
Ludvik B.,
Milicevic Z.,
Peña A.,
Shurzinske L.,
Karanikas C. A.,
Pechtner V.
Publication year - 2016
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12671
Subject(s) - dulaglutide , postprandial , medicine , metformin , endocrinology , type 2 diabetes , insulin , glucagon , glucagon like peptide 1 receptor , area under the curve , insulin resistance , agonist , diabetes mellitus , exenatide , receptor
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 [ AUC glucose (0–3 h)] were observed among all groups. β ‐cell function [ AUC insulin / AUC glucose (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.