Adjunctive Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of Type 1 Diabetes Mellitus

Pharmacotherapy. 2016 Sep;36(9):1011-20. doi: 10.1002/phar.1804. Epub 2016 Sep 1.


Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used in combination with insulin to manage type 2 diabetes mellitus, and four agents are currently approved for this indication: exenatide, liraglutide, dulaglutide, and albiglutide. The distinctive properties of GLP-1 RAs-potential hemoglobin A1c (A1C) reduction, weight loss, potential to reduce insulin doses, and lower hypoglycemia risk-have made these agents potential treatment options for patients with type 1 diabetes mellitus (T1DM) as well. These positive effects are due to glucose-dependent insulin secretion, reduced glucagon secretion, increased satiety, and delayed gastric emptying. Patients with T1DM are unable to suppress glucagon during meals, which contributes to postprandial hyperglycemia and may be improved with GLP-1 therapy. In this review, we evaluated the available literature on the clinical efficacy and safety of GLP-1 RAs in patients with T1DM. We conducted a search of the PubMed (1966-May 2016) and Ovid (1946-May 2016) databases. Abstracts presented at the scientific and clinical sessions of the American Diabetes Association and the American Association of Clinical Endocrinologists were also searched. The references of the published articles were also reviewed to identify additional studies appropriate for inclusion. All identified articles published in English were evaluated. Studies were included if they evaluated the clinical use or safety of GLP-1 RAs in patients with T1DM. Twelve studies were included, with four evaluating exenatide, one evaluating exenatide extended release, and seven evaluating liraglutide. Both exenatide and liraglutide showed significant reductions in hemoglobin A1C, plasma glucose concentration, body weight, and insulin doses when administered to patients with T1DM already receiving insulin therapy, without increasing the occurrence of hypoglycemia. Adverse effects were mostly gastrointestinal in nature but were mild and transient. Patients who may benefit most are those experiencing adverse effects from insulin, those not at their A1C goal but hypoglycemia prevents insulin titration, and those who may benefit from weight loss.

Keywords: exenatide; glucagon-like peptide-1 receptor agonists; liraglutide; type 1 diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Exenatide
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glycated Hemoglobin A / analysis
  • Humans
  • Liraglutide / therapeutic use
  • Peptides / adverse effects
  • Peptides / therapeutic use
  • Venoms / adverse effects
  • Venoms / therapeutic use


  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Peptides
  • Venoms
  • hemoglobin A1c protein, human
  • Liraglutide
  • Exenatide