Short-acting glucagon-like peptide-1 receptor agonists as add-on to insulin therapy in type 1 diabetes: A review

Diabetes Obes Metab. 2017 Jul;19(7):915-925. doi: 10.1111/dom.12911. Epub 2017 Mar 17.


A large proportion of patients with type 1 diabetes do not reach their glycaemic target of glycated hemoglobin (HbA1c) <7.0% (53 mmol/mol) and, furthermore, an increasing number of patients with type 1 diabetes are overweight and obese. Treatment of type 1 diabetes is based on insulin therapy, which is associated with well-described and unfortunate adverse effects such as hypoglycaemia and increased body weight. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are the focus of increasing interest as a possible adjunctive treatment to insulin in type 1 diabetes because of their glucagonostatic and extrapancreatic effects. So far, the focus has mainly been on the long-acting GLP-1RAs, but the risk-benefit ratio emerging from studies evaluating the effect of long-acting GLP-1RAs as adjunctive therapy to insulin therapy in patients with type 1 diabetes has been disappointing. This might be attributable to a lack of glucagonostatic effect of these long-acting GLP-1RAs in type 1 diabetes, alongside development of tachyphylaxis to GLP-1-induced retardation of gastric emptying. In contrast, the short-acting GLP-1RAs seem to have a preserved and sustained effect on glucagon secretion and gastric emptying in patients with type 1 diabetes, which could translate into effective lowering of postprandial glucose excursions; however, these observations regarding short-acting GLP-1RAs are all derived from small open-label trials and should thus be interpreted with caution. In the present paper we review the potential role of GLP-1RAs, in particular short-acting GLP-1RAs, as add-on to insulin in the treatment of type 1 diabetes.

Keywords: GLP-1 analogue; antidiabetic drug; glucagon; incretin therapy; insulin therapy; type 1 diabetes.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Drug Resistance
  • Drug Therapy, Combination / adverse effects
  • Exenatide
  • Gastric Emptying / drug effects
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glycated Hemoglobin A / analysis
  • Half-Life
  • Humans
  • Hyperglycemia / prevention & control*
  • Hypoglycemia / chemically induced
  • Hypoglycemia / prevention & control
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / adverse effects
  • Insulin / blood
  • Insulin / pharmacokinetics
  • Insulin / therapeutic use*
  • Peptides / adverse effects
  • Peptides / blood
  • Peptides / pharmacokinetics
  • Peptides / therapeutic use*
  • Venoms / adverse effects
  • Venoms / blood
  • Venoms / pharmacokinetics
  • Venoms / therapeutic use*


  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Peptides
  • Venoms
  • hemoglobin A1c protein, human
  • lixisenatide
  • Exenatide