The effect of addition of liraglutide to high-dose intensive insulin therapy: a randomized prospective trial

Diabetes Obes Metab. 2014 Sep;16(9):827-32. doi: 10.1111/dom.12286. Epub 2014 Mar 25.


Aims: Patients with type 2 diabetes and insulin resistance may require high insulin doses to control hyperglycaemia. The addition of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to basal insulin therapy has been shown to reduce insulin requirement while reducing insulin-associated weight gain [1,2]. The effect of GLP-1 RA therapy added to intensive (basal/bolus) insulin therapy has not been studied in a prospective trial. This trial evaluated the effect of the addition of liraglutide to high-dose intensive insulin therapy compared with standard insulin up-titration in obese insulin-resistant patients with type 2 diabetes requiring high-dose insulin therapy.

Methods: Thirty-seven subjects with type 2 diabetes requiring >100 units of insulin daily administered either by continuous subcutaneous insulin infusion (CSII) or by multiple daily injections (MDIs) with or without metformin were randomized to receive either liraglutide plus insulin (LIRA) or intensive insulin only (controls). Liraglutide was initiated at 0.6 mg subcutaneously (sq) per day and increased to either 1.2 or 1.8 mg daily in combination with intensive insulin therapy. Controls received intensive insulin up-titration only.

Results: At 6 months, subjects receiving liraglutide plus insulin experienced statistically significant reductions in HbA1c, weight, insulin dose and glycaemic variability (GV) by continuous glucose monitor (CGM) compared with the control group receiving insulin only.

Conclusions: Adding liraglutide to intensive high-dose (basal/bolus) insulin therapy results in greater improvement in glycaemic control than insulin therapy alone, with additional benefits of weight loss and reduced GV.

Keywords: GLP-1 analogue; insulin intensive management; insulin resistance; insulin therapy; type 2 diabetes.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Blood Glucose / metabolism
  • Body Mass Index
  • Body Weight
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / therapeutic use*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / drug therapy*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage
  • Insulin / therapeutic use*
  • Liraglutide / administration & dosage
  • Liraglutide / therapeutic use*
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / complications
  • Prospective Studies
  • Treatment Outcome


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • hemoglobin A1c protein, human
  • Liraglutide
  • Glucagon-Like Peptide 1