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

Abstract

ObjectiveLoss 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/methodsWe studied 80 T2D patients inadequately controlled [glycosylated hemoglobin (HbA1c), 7.0%–9.5%] receiving stable metformin for ≥12weeks. 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 20mg (n=21, 19, or 19), or placebo (n=21), plus metformin, for 8weeks. We measured postprandial plasma glucose (PPG) and insulin profiles, insulin secretion rate (ISR), oral glucose insulin sensitivity (OGIS) index; β-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios, and insulin sensitivity-to-insulin resistance (or disposition) index. ResultsAfter 8 weeks of treatment, taspoglutide 5, 10, and 20mg QW doses vs. placebo improved mean PPG0–240 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% vs. +1%; P<0.005 vs dose). Taspoglutide at 20mg QW dose also resulted in improvements from baseline in OGIS, β-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios and the disposition index during the MTT. ConclusionTaspoglutide QW significantly improved pancreatic function in patients with T2D treated with metformin.