Effect of Liraglutide on Times in Glycaemic Ranges as Assessed by CGM for Type 2 Diabetes Patients Treated With Multiple Daily Insulin Injections

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Introduction: The effects of the GLP-1 analogue liraglutide on time in hypoglycaemia, time in hyperglycaemia, and time in range for type 2 diabetes patients initially treated with multiple daily insulin injections (MDI) were investigated. Variables associated with hypoglycaemia in the current population were also identified. Methods: Analyses were based on data from a previously performed double-blind, placebo-controlled trial in which 124 MDI-treated patients with type 2 diabetes were randomized to liraglutide or placebo. Masked continuous glucose monitoring (CGM) was performed at baseline and week 24 in 99 participants. Results: The mean time in hypoglycaemia was similar for participants receiving liraglutide and those receiving placebo after 24 weeks of treatment. Mean time in target was greater in the liraglutide group than in the placebo group: 430 versus 244 min/24 h (p < 0.001) and 960 versus 695 min/24 h (p < 0.001) for the two glycaemic ranges considered, 4–7 mmol/l and 4–10 mmol/l, respectively. Mean time in hyperglycaemia was lower in the liraglutide group: 457 versus 723 min/24 h (p = 0.001) and 134 versus 264 min/24 h (p = 0.023) for the two cutoffs considered, > 10 mmol/l and > 14 mmol/l, respectively. Lower mean glucose level, lower C-peptide, and higher glucose variability were associated with an increased risk of hypoglycaemia in both treatment groups. Higher proinsulin level was associated with a lower risk of hypoglycaemia in the liraglutide group. Conclusion: For type 2 diabetes patients initially treated with MDI, introducing liraglutide had a beneficial effect on glucose profiles estimated by masked CGM. Mean glucose level, glycaemic variability, C-peptide, and proinsulin level influenced the risk of hypoglycaemia in this population. Trial Registration: ClinicalTrials.gov, number (EudraCT nr: 2012-001941-42). Funding: Novo Nordisk funded this study. The Diabetes Research Unit, NU-Hospital Group funded the journal’s Rapid Service Fee.


  • Sheyda Sofizadeh
  • Henrik Imberg
  • Arndís F. Ólafsdóttir
  • Magnus Ekelund
  • Sofia Dahlqvist
  • Irl Hirsch
  • Karin Filipsson
  • Bo Ahrén
  • Stefan Sjöberg
  • Jaako Tuomilehto
  • Marcus Lind
External organisations
  • University of Gothenburg
  • Chalmers University of Technology
  • Novo Nordisk A/S
  • University of Washington
  • Karolinska University Hospital
  • Finnish National Institute for Health and Welfare
  • University of Helsinki
  • King Abdulaziz University
  • NU Hospital Group
  • Statistiska Konsultgruppen
  • Karolinska Institutet
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes


  • Continuous glucose monitoring, Hyperglycaemia, Hypoglycaemia, Liraglutide, Placebo, Randomized clinical trial, Time in range, Type 2 diabetes mellitus
Original languageEnglish
Pages (from-to)2115-2130
JournalDiabetes Therapy
Issue number6
Early online date2019 Sep 28
Publication statusPublished - 2019
Publication categoryResearch