Glucagon-like peptide 1 receptor agonists in type 1 diabetes mellitus

Abstract

Purpose: The role of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in the treatment of type 1 diabetes mellitus (T1DM), including efficacy and safety evidence, is reviewed.

Summary: Currently approved treatment options for glycemic control in T1DM include insulin, which combats insulin deficiency but does not effectively target disease progression or alpha cell dysfunction; and pramlintide, whose use requires multiple daily doses and involves a high likelihood of gastrointestinal side effects. GLP-1 RAs have a unique mechanism of action in T1DM, addressing alpha cell dysfunction and thereby suppressing inappropriate glucagon secretion. GLP-1 RA dosing varies from once weekly to twice daily, and the class is well tolerated in patients with type 2 diabetes. Among the GLP-1 RAs, exenatide and liraglutide have been studied in patients with T1DM, with published evidence consistently demonstrating weight loss, decreases in total daily insulin requirements, and modest improvements in glycemic control. GLP-1 RA therapy appears to be well tolerated in patients with T1DM and is associated with nonsignificant increases in hypoglycemia risk.

Conclusion: GLP-1 RA therapy represents an important add-on therapy option for achieving decreased insulin doses, weight loss, and modest improvements in HbA1c levels without significantly increasing hypoglycemia risk in patients with T1DM. Patients who have detectable C-peptide and/or are overweight or cannot achieve glycemic goals without hypoglycemia have been found to benefit the most from GLP-1 RA therapy. Further studies are warranted to evaluate these agents' potential impact on clinical outcomes such as microvascular and macrovascular complications.

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