1034-P: Liraglutide and Dapagliflozin Induce an Increase in Plasma GLP-1 and GLP-2 Concentrations

Since liraglutide suppresses plasma glucagon concentrations and dapagliflozin increases glucagon concentrations, although both improve glycemia in patients with type 1 diabetes, we have now investigated whether they alter the concentrations of the two other products of the proglucagon gene, GLP-1 and GLP-2. Thirty patients with type 1 diabetes, treated with liraglutide for 26 weeks were randomized into receiving dapagliflozin 10 mg daily (n=20) or placebo (n=10) for 12 weeks. Fasting blood samples were obtained prior to liraglutide treatment, at the onset of dapagliflozin treatment and at the end of dapagliflozin treatment. At the end of 26 weeks liraglutide treatment and then 12 weeks of dapagliflozin therapy, mean HbA1c fell by 0.31±0.19% (NS) and 0.66±0.22% (p=0.0004), respectively. There was a significant increase in the plasma concentrations of GLP-1 (by 89±24%, from 30.4±5.1pM to 48.6±8.2pM, P=0.001) but not GLP-2 after 26 weeks of liraglutide treatment with a fall in glucagon levels. Dapagliflozin treatment induced a further significant increase in plasma GLP-1 (by 72±24%, from 48.6±8.2pM to 70.8±9.2pM, P=0.001) and caused an increase in GLP-2 concentrations (by 48±18%, from 2.01±0.42ng/ml to 2.97±0.51pM, P=0.01) along with an increase in glucagon concentrations. We conclude that while liraglutide suppresses glucagon, it induces an increase in GLP-1 concentrations. In addition, dapagliflozin increases both GLP-1 and GLP-2 concentrations while also increasing glucagon.