Glucagon-like peptide-1 agonists: Role of the gut in hypoglycemia unawareness, and the rationale in type 1 diabetes.

Type 1 diabetes is increasing and the majority of patients have poor glycemic control. Although advanced technology and nanoparticle use have greatly enhanced insulin delivery and glucose monitoring, weight gain and hypoglycemia remain major challenges and a constant source of concern for patients with type 1 diabetes. Type 1 diabetes shares some pathophysiology with type 2 diabetes, and an overlap has been reported. The above observation created great interest in glucagon-like peptide-1 receptor agonists (GLP-1) as adjuvants for type 1 diabetes. Previous trials confirmed the positive influence of GLP-1 agonists on β cell function. However, hypoglycemia unawareness and dysregulated glucagon response have been previously reported in patients with recurrent hypoglycemia using GLP-1 agonists. Jin et al found that the source of glucagon dysregulation due to GLP-1 agonists resides in the gut. Plausible explanations could be gut nervous system dysregulation or gut microbiota disruption. This review evaluates the potential of GLP-1 agonists in managing type 1 diabetes, particularly focusing on their impact on glycemic control, weight management, and glucagon dysregulation. We provide a broader insight into the problem of type 1 diabetes mellitus management in the light of recent findings and provide future research directions.