Eight weeks of treatment with long-acting GLP-1 analog taspoglutide improves postprandial insulin secretion and sensitivity in metformin-treated patients with type 2 diabetes

Objective. Loss of pancreatic function is pivotal to the deterioration of fasting and postprandial glycemic control in type 2 diabetes (T2D). We evaluated the effects of a long-acting, human glucagon-like peptide-1 analog, taspoglutide, added to metformin, on pancreatic function and peripheral insulin sensitivity. Materials/methods. We studied 80 T2D patients inadequately controlled [glycosylated hemoglobin (HbA(1c)), 7.0%-9.5%] receiving stable metformin for >= 12 weeks. They were a subset of participants to a phase 2 trial that received also a 240-min mixed-meal tolerance test (MTT) at baseline and study end. Patients received once weekly (QW) sc injection of taspoglutide 5, 10, or 20 mg (n = 21, 19, or 19), or placebo (n = 21), plus metformin, for 8 weeks. We measured postprandial plasma glucose (PPG) and insulin profiles, insulin secretion rate (ISR), oral glucose insulin sensitivity (OGIS) index; beta-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios, and insulin sensitivity-to-insulin resistance (or disposition) index. Results. After 8 weeks of treatment, taspoglutide 5, 10, and 20 mg QW doses us. placebo improved mean PPG(0-240 min) (relative change from baseline: -22.1%, -25.9%, and -22.9% vs. -8.1%; P < 0.005) and mean postprandial ISR0-240 min (+14%, +18%, and +23% us. +1%; P < 0.005 vs dose). Taspoglutide at 20 mg QW dose also resulted in improvements from baseline in OGIS, beta-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios and the disposition index during the MTT. Conclusion. Taspoglutide QW significantly improved pancreatic function in patients with T2D treated with metformin. (C) 2013 Elsevier Inc. All rights reserved.