Mechanisms of Action of Liraglutide in Patients with Type 2 Diabetes Treated with High Dose Insulin

Context: The mechanisms of action of incretin mimetics in patients with long-standing type 2 diabetes (T2D) and high insulin requirements have not been studied. Objective: To evaluate changes in β-cell function, glucagon secretion, and fat distribution after addition of liraglutide to high-dose insulin. Design: A single-center, randomized, double-blind, placebo-controlled trial. Setting: University of Texas Southwestern and Parkland Memorial Hospital clinics. Patients: Seventy-one patients with long-standing (median, 17 years) T2D requiring high-dose insulin treatment (>1.5 U/kg/d; average, 2.2 ± 0.9 U/kg/d). Intervention: Patients were randomized to liraglutide 1.8 mg/d or matching placebo for 6 months. Main Outcome Measures: We measured changes in insulin and glucagon secretion using a 4-hour mixed-meal challenge test. Magnetic resonance-based techniques were used to estimate sc and visceral fat in the abdomen and ectopic fat in the liver and pancreas. Results: Glycosylated hemoglobin improved significa...