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)
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. 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). Of 50 randomised patients (mean age 58 years, BMI 33 kg/m2, 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. 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 ClinicalTrials.gov NCT01392898 Funding The study was funded by Novo Nordisk.