Clinical Efficacy and Safety of Once-Weekly Glucagon-Like Peptide-1 Agonists in Development for Treatment of Type 2 Diabetes Mellitus in Adults

Abstract

Spanish

French

OBJECTIVE:

To review pharmacologic, pharmacokinetic, efficacy, and safety data of once-weekly glucagon-like peptide-1 (GLP-1) agonists exenatide long-acting release (LAR), albiglutide, and taspoglutide in treatment of type 2 diabetes mellitus (T2DM).

DATA SOURCES:

A MEDLINE search (1966-August 2011) was conducted using the following key words: type 2 diabetes mellitus, glucagon-like peptide-1 agonists once weekly, glucagon-like peptide-1 agonists, exenatide LAR, albiglutide, and taspoglutide.

STUDY SELECTION AND DATA EXTRACTION:

All articles published in English identified from the data sources were evaluated, prioritizing randomized controlled trials with human data. The references of published articles identified were examined for additional studies appropriate for the review.

DATA SYNTHESIS:

Native GLP-1 increases glucose-dependent insulin secretion, decreases glucagon secretion, and slows gastric emptying in healthy individuals, but these effects may be blunted in patients with T2DM. Because native GLP-1 is rapidly degraded by dipeptidyl peptidase-IV, it is not a practical treatment option. Currently, 2 GLP-1 receptor agonists have been approved by the Food and Drug Administration: exenatide twice daily and liraglutide once daily. Several additional GLP-1 agonists, including exenatide LAR, albiglutide, and taspoglutide, are in various stages of clinical trials and have been modified to increase their half-lives. These agents have shown significant improvements in hemoglobin A_1c, fasting plasma glucose, and postprandial plasma glucose, as well as improvements in body weight, blood pressure, and lipid parameters. These agents allow for less-frequent dosing schedules, improved glycemic control throughout the day, and improved treatment satisfaction compared to some available agents. GLP-1 agonists have been well tolerated, with the most common adverse effects being gastrointestinal related, which occurred early in therapy but typically resolved after 4-8 weeks. The incidence of hypoglycemia was infrequent and mild during therapy.

CONCLUSIONS:

Once-weekly GLP-1 agonists provide similar glycemic control with weight reduction, as well as overall higher treatment satisfaction for patients because of their ease of use and need for less-frequent dosing compared to some available agents.

Keywords

albiglutide exenatide LAR glucagon-like peptide-1 agonist taspoglutide type 2 diabetes mellitus

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