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

Diabetes Obes Metab. 2017 Sep;19(9):1306-1311. doi: 10.1111/dom.12944. Epub 2017 May 18.

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.

Keywords: insulin; ketogenesis; liraglutide; type 1 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / metabolism
  • Double-Blind Method
  • Drug Resistance
  • Drug Therapy, Combination
  • Fatty Acids, Nonesterified / antagonists & inhibitors
  • Fatty Acids, Nonesterified / blood
  • Female
  • Ghrelin / antagonists & inhibitors
  • Ghrelin / blood
  • Glucagon / antagonists & inhibitors*
  • Glucagon / blood
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use*
  • Injections, Subcutaneous
  • Insulin / administration & dosage
  • Insulin / therapeutic use
  • Insulin Infusion Systems
  • Ketone Bodies / antagonists & inhibitors*
  • Ketone Bodies / biosynthesis
  • Ketone Bodies / blood
  • Lipolysis / drug effects*
  • Liraglutide / administration & dosage
  • Liraglutide / therapeutic use*
  • Male
  • Middle Aged

Substances

  • Fatty Acids, Nonesterified
  • GHRL protein, human
  • GLP1R protein, human
  • Ghrelin
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Insulin
  • Ketone Bodies
  • Liraglutide
  • Glucagon