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

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 (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.

RESULTS:

After 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.

CONCLUSION:

Taspoglutide QW significantly improved pancreatic function in patients with T2D treated with metformin.

• Authors: Amalia Gastaldelli, Michael A Nauck, Raffaella Balena
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 62 Issue 9 Pg. 1330-9 (Sep 2013) ISSN: 1532-8600 [Electronic] United States
• PMID: 23831441 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Insulin
• Peptides
• taspoglutide
• Metformin

Topics

• Adolescent
• Adult
• Aged
• Blood Glucose (analysis)
• Diabetes Mellitus, Type 2 (drug therapy, metabolism)
• Female
• Humans
• Hypoglycemic Agents (therapeutic use)
• Insulin (metabolism)
• Insulin Secretion
• Male
• Metformin (therapeutic use)
• Middle Aged
• Peptides (therapeutic use)
• Postprandial Period (physiology)