Differential effects of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide and metformin on pancreatic beta-cell and insulin sensitivity during a standardized test meal in patients with type 2 diabetes

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. beta-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. beta-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 beta-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 beta-cell function, while metformin exerts a greater effect on insulin sensitivity.