Clinical efficacy and safety of once-weekly glucagon-like peptide-1 agonists in development for treatment of type 2 diabetes mellitus in adults.
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).


METHODS
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.


METHODS
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.


RESULTS
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.
Cabarrus Family Medicine, Harrisburg, NC, USA. m.tzefos@wingate.edu
Maria
M
Tzefos
Kira
K
Harris
Adriane
A
Brackett
D000328:Adult; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000819:agonists* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; C541736:taspoglutide; C534611:rGLP-1 protein; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide