Liraglutide acutely suppresses glucagon, lipolysis and ketogenesis in type 1 diabetes

In view of the occurrence of diabetic ketoacidosis associated with the use of SGLT2 inhibitors in patients with type 1 diabetes (T1DM) and absence of this complication in patients treated with liraglutide in spite of reductions in insulin doses, we investigated the effect of liraglutide on ketogenesis. Twenty six patients with inadequately controlled T1DM (age:43.8±3.9 years; HbA1c:7.7±0.3%

, BMI:

31.8±1.8Kg/m2), treated with CSII were randomly divided into two groups of 13 patients each. After an overnight fast, patients were injected with either liraglutide 1.8mg or with placebo. They were maintained on their basal insulin infusion and were followed up for 5 hours. The patients injected with placebo maintained their glucose and glucagon concentrations without an increase but there was a significant increase in FFA (from 0.35±0.06 to 0.49±0.07Mm), acetoacetate (from 0.41±0.04 to 0.68±0.10mM) and &bgr;-hydoxybutyrate (from 0.29±0.06 to 0.57±0.19mM) and ghrelin (from 288±28 to 362±35pg/ml) concentrations (p<0.05 for all). In contrast, liraglutide significantly suppressed glucose (from 173±21 to 135±18mg/dl) and glucagon (from 91±15 to 72±13pg/ml) concentrations, reduced the increases in FFA (by 39±14%), and totally prevented the increase in ghrelin, acetoacetate and phydroxybutyrate concentrations. There was no significant change in hormone sensitive lipase or in lipoprotein lipase plasma levels in either group. Our data show clearly that while the peripheral insulin concentrations in inadequately controlled T1 DM was sufficient for maintaining steady glucose concentrations, though at an elevated level, do not provide enough insulin to prevent the increase in concentrations of ghrelin, FFA, acetoacetate and p-hydroxybutyrate. These changes are prevented by single a dose of liraglutide. We conclude that acute treatment with liraglutide suppresses ghrelin, glucagon, lipolysis and ketogenesis. These observations are relevant to the use of liraglutide in the management of T1 DM.