title: Liraglutide acutely suppresses glucagon, lipolysis and ketogenesis in type 1 diabetes.
abstract: In view of the occurrence of diabetic ketoacidosis associated with the use of sodium-glucose transport protein-2 inhibitors in patients with type 1 diabetes (T1DM) and the relative 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 were randomly divided into 2 groups of 13 patients each. After an overnight fast, patients were injected, subcutaneously, with either liraglutide 1.8 mg or with placebo. They were maintained on their basal insulin infusion and were followed up in our clinical research unit for 5 hours. The patients injected with placebo maintained their glucose and glucagon concentrations without an increase, but there was a significant increase in free fatty acids (FFA), acetoacetate and β-hydoxybutyrate concentrations. In contrast, liraglutide significantly reduced the increase in FFA, and totally prevented the increase in acetoacetate and β-hydroxybutyrate concentrations while suppressing glucagon and ghrelin concentrations. Thus, a single dose of liraglutide is acutely inhibitory to ketogenesis.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Manisha
authors.initials: M
authors.lastname: Garg
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Husam
authors.initials: H
authors.lastname: Ghanim
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Nitesh D
authors.initials: ND
authors.lastname: Kuhadiya
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Kelly
authors.initials: K
authors.lastname: Green
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Hejna
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Abuaysheh
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Barrett
authors.initials: B
authors.lastname: Torre
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Manav
authors.initials: M
authors.lastname: Batra
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Antoine
authors.initials: A
authors.lastname: Makdissi
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Ajay
authors.initials: A
authors.lastname: Chaudhuri
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Paresh
authors.identifier: 0000-0002-7055-2084
authors.initials: P
authors.lastname: Dandona
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005230:Fatty Acids, Nonesterified / Q000037:antagonists & inhibitors / Q000097:blood; D005260:Female; D054439:Ghrelin / Q000037:antagonists & inhibitors / Q000097:blood; D005934:Glucagon / Q000037:antagonists & inhibitors* / Q000097:blood; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D007657:Ketone Bodies / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood; D008066:Lipolysis / Q000187:drug effects*; D000069450:Liraglutide / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D005230:Fatty Acids, Nonesterified; C515349:GHRL protein, human; C000593833:GLP1R protein, human; D054439:Ghrelin; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007328:Insulin; D007657:Ketone Bodies; D000069450:Liraglutide; D005934:Glucagon; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: insulin; ketogenesis; liraglutide; type 1 diabetes