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). 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 ClinicalTrials.gov NCT01392898 Funding The study was funded by Novo Nordisk.
Results
The number of inaccurate breath holds was unacceptably high, moreover, these could not be identified from CBFV registrations alone. Therefore, reports of CR based on breath holds in older subjects without coregistration of BP and either end-tidal CO(2) or chest-expansion should no longer be acceptable.
In T2DM patients with pronounced insulin-associated weight gain, addition of liraglutide within 2 years leads to sustained reversal of body weight, improved glycaemic control and decrease in insulin dose. Thus, liraglutide offers a valuable therapeutic option.
The response to placebo treatment was related to its active comparator, with injectable placebo GLP-1ra showing a relevant response on weight, whereas oral placebo DPP4i showed no significant response. These findings may suggest that subjective expectations influence T2DM treatment efficacy, which can possibly be employed therapeutically.
Administration of rapid-acting insulin by jet injection results in faster correction of marked hyperglycaemia in overweight or obese patients with insulin-requiring diabetes.
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