745-P: Effects of Liraglutide on GLP-1, GIP, and Glucagon Concentrations in Persons with Type 2 Diabetes with Multiple Daily Insulin Injections during a 24-Week Period

Introduction and Objective: Although there is extensive knowledge of metabolic and cardiovascular effects of GLP-1 analogues, placebo-controlled trials are sparse examining how endogenous incretins are affected during therapy. The aim of this study was to evaluate the concentrations of GLP-1, GIP and glucagon in liraglutide treated persons with type 2 diabetes (T2D) and associations with changes in glycemic control.

Methods: The current analysis included 106 patients with available biobank samples of the 124 persons with T2D who took part in the double-blind placebo-controlled MDI liraglutide trial. Differences in GLP-1, GIP and glucagon between treatment groups were evaluated using analysis of covariance, adjusting for baseline values. Linear regression was used to evaluate baseline concentrations of GLP-1, GIP, and glucagon as possible predictors for a greater or smaller treatment effect of liraglutide on HbA1c.

Results: At 12 weeks GLP-1 was 25% lower (95% CI 9-37%, p=0.003) and GIP 39% higher (95% CI 8-79%, p=0.012) in the liraglutide group compared to the placebo group. At 24 weeks differences were sustained. Glucagon was lower in the liraglutide group at 12 weeks (p=0.052) but reached similar levels as the placebo group after 24 weeks (p=0.98). In the liraglutide group mean Hba1c decreased from 9.0% to 7.4%. Each 30% decrease in glucagon concentration at baseline was associated with 0.3% greater reduction in HbA1c at 24 weeks of treatment with liraglutide compared to placebo (95% CI 0.1-0.5%, p=0.001).

Conclusion: An essential mechanism of metabolic effects of GLP-1 analogues is potentially mediated via increased GIP levels in persons with T2D. According to our findings serum glucagon levels may be an important biomarker for GLP-1 analogue responders.