Liraglutide reverses pronounced insulin-associated weight gain, improves glycaemic control and decreases insulin dose in patients with type 2 diabetes: a 26 week, randomised clinical trial (ELEGANT)

Diabetologia. 2014 Sep;57(9):1812-9. doi: 10.1007/s00125-014-3302-0. Epub 2014 Jun 20.


Aims/hypothesis: The best treatment strategy for a patient with type 2 diabetes who shows pronounced weight gain after the introduction of insulin treatment is unclear. We determined whether addition of a glucagon-like peptide-1 (GLP-1) analogue could reverse pronounced insulin-associated weight gain while maintaining glycaemic control, and compared this with the most practised strategy, continuation and intensification of standard insulin therapy.

Methods: In a 26-week, randomised controlled trial (ELEGANT), conducted in the outpatient departments of one academic and one large non-academic teaching hospital in the Netherlands, adult patients with type 2 diabetes with ≥ 4% weight gain during short-term (≤ 16 months) insulin therapy received either open-label addition of liraglutide 1.8 mg/day (n = 26) or continued standard therapy (n = 24). A computer-generated random number list was used to allocate treatments. Participants were evaluated every 4-6 weeks for weight, glycaemic control and adverse events. The primary endpoint was between-group weight difference after 26 weeks of treatment (intention to treat).

Results: Of 50 randomised patients (mean age 58 years, BMI 33 kg/m(2), HbA1c 7.4% [57 mmol/mol]), 47 (94%) completed the study; all patients were analysed. Body weight decreased by 4.5 kg with liraglutide and increased by 0.9 kg with standard therapy (mean difference -5.2 kg [95% CI -6.7, -3.6 kg]; p < 0.001). The respective changes in HbA1c were -0.77% (-8.4 mmol/mol) and +0.01% (+0.1 mmol/mol) (difference -0.74% [-8.1 mmol/mol]) ([95% CI -1.08%, -0.41%] [-11.8, -4.5 mmol/mol]; p < 0.001); respective changes in insulin dose were -29 U/day and +5 U/day (difference -33 U/day [95% CI -41, -25 U/day]; p < 0.001). In five patients (19%), insulin could be completely discontinued. Liraglutide was well tolerated; no severe adverse events or severe hypoglycaemia occurred.

Conclusions/interpretation: In patients with pronounced insulin-associated weight gain, addition of liraglutide to their treatment regimen reverses weight, decreases insulin dose and improves glycaemic control, and hence seems a valuable therapeutic option compared with continuation of standard insulin treatment. Trial registration NCT01392898. Funding The study was funded by Novo Nordisk.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / drug effects*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage*
  • Insulin / therapeutic use*
  • Liraglutide
  • Male
  • Middle Aged
  • Weight Gain / drug effects*


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Liraglutide
  • Glucagon-Like Peptide 1

Associated data