An update in incretin-based therapy: a focus on glucagon-like peptide-1 receptor agonists

Diabetes Technol Ther. 2012 Oct;14(10):951-67. doi: 10.1089/dia.2012.0098.edw. Epub 2012 Jul 30.

Abstract

The glucagon-like peptide-1 receptor agonists, exenatide and liraglutide, offer a unique mechanism in the treatment of type 2 diabetes mellitus (T2DM) as part of the incretin system. Their mechanism of action is to increase insulin secretion, decrease glucagon release, reduce food intake, and slow gastric emptying. They target postprandial blood glucose values and have some effect on fasting levels as well. In addition, they promote weight loss and may help to preserve β-cell function, both major problems in T2DM patients. Changes in hemoglobin A1c are similar to those produced by other T2DM agents, including thiazolidinediones, low-dose metformin, and sulfonylureas, and better than those caused by α-reductase inhibitors and dipeptidyl peptidase-4 inhibitors. These agents have been safely studied in combination with metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin therapy. Overall, data are limited for head-to-head comparisons, but it appears that liraglutide may have better efficacy and tolerability compared with exenatide; however, more studies are needed. They are overall well tolerated, with the main adverse events being similar to those with metformin (gastrointestinal intolerances that are transient and dose dependent). However, patients must be monitored for pancreatitis as a rare but possible side effect. For T2DM patients willing to use an injectable agent, exenatide and liraglutide offer another therapeutic option to control hyperglycemia with the potential for weight loss and may be combined with other agents safely.

Publication types

  • Review

MeSH terms

  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Exenatide
  • Female
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / drug effects*
  • Glucagon-Like Peptide 1 / pharmacology
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A / drug effects
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Liraglutide
  • Male
  • Peptides / pharmacology*
  • Receptors, Glucagon / agonists*
  • Treatment Outcome
  • Venoms / pharmacology*

Substances

  • Blood Glucose
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • Receptors, Glucagon
  • Venoms
  • hemoglobin A1c protein, human
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Exenatide