Long-Term Glycemic Outcomes and the Evaluation of the Insulin Response to Glucagon Stimulation Before and After the Administration of Liraglutide, a Glucagon-like Peptide-1 Receptor Agonist

Abstract

The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide was administered at 0.9 mg/day to 34 Japanese patients with type 2 diabetes mellitus receiving insulin, oral hypoglycemic agents, or combination therapy, and the endogenous insulin secretory capacity in response to intravenous glucagon administration (change in C-peptide immunoreactivity ΔCPR and C-peptide index (CPI; a measure of fasting C-peptide secretion) were measured before and after the administration. The relationship between liraglutide administration and glycemic control indicators for up to 24 months was also investigated. Hemoglobin A1c (HbA1c) levels decreased significantly after three months and did not change greatly thereafter. A negative correlation was observed between the ΔCPR before treatment initiation and the change in HbA1c after 24 months. The CPI improved significantly at 12 months after treatment initiation, and the ΔCPR decreased significantly compared to before treatment initiation. These findings indicate that performing a glucagon loading test to determine the endogenous insulin secretory capacity prior to the initiation of GLP-1 receptor agonist therapy in Japanese patients with type 2 diabetes mellitus may be effective for predicting the efficacy of liraglutide. These findings also suggest that liraglutide administration increases the fasting endogenous insulin secretion.