Safety, efficacy and tolerability of exenatide in combination with insulin in the Association of British Clinical Diabetologists nationwide exenatide audit*

Thong, K. Y.; Jose, Biju; Sukumar, Nithya; Cull, ML; Mills, A. P.; Sathyapalan, Thozhukat; Shafiq, Waqas; Rigby, Alan S.; Walton, Chris; Ryder, Robert E.

doi:10.1111/j.1463-1326.2011.01393.x

Cited by 85 publications

(96 citation statements)

References 23 publications

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“…Some previous studies, mostly observational, have investigated the effect of adding GLP-1 analogues to existing insulin treatment in patients with type 2 diabetes [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Our study differs from previous randomised controlled trials (RCTs) in that this is the first RCT where liraglutide was added to reverse weight gain in fairly well controlled patients, while all other trials added GLP-1 analogues to improve glycaemic control, and reported results on body weight as secondary outcomes, showing mixed results [16,17,19,23,[25][26][27].…”

Section: Discussionmentioning

confidence: 99%

“…However, GLP-1 analogues are expensive, have gastrointestinal side effects, and lack long-term safety and efficacy data, which renders it important to select those patients that are most likely to benefit from this therapy. Previous studies on the combination of GLP-1 analogues and insulin all focused on glycaemic benefit, with some reporting additional weight loss and others stable body weight [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Furthermore, most studies are either placebo controlled or observational and do not compare clinically relevant treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

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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)

et al. 2014

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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

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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)

et al. 2014

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“…However, in clinical trials examining GLP-1 receptor agonists in combination with sulphonylurea (with or without metformin) or insulin, the incidence of hypoglycemia, although low overall, was increased compared with placebo ( Table 6, in the Appendix) [32,33,42,[123][124][125][126][127][128][129][130][131][132][133][134][135]. Interestingly, the concomitant administration of GLP-1 receptor agonists with a sulphonylurea in the in situ perfused rat pancreas led to uncoupling of the insulinotropic effect of GLP-1 from its glucose dependence [136].…”

Section: Endocrine Effectsmentioning

confidence: 99%

Adverse Effects of GLP-1 Receptor Agonists

2014

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■ AbstractGlucagon-like peptide-1 (GLP-1) receptor agonists are a class of injective anti-diabetic drugs that improve glycemic control and many other atherosclerosis-related parameters in patients with type 2 diabetes (T2D). However, the use of this relatively new class of drugs may be associated with certain adverse effects. Concerns have been expressed regarding the effects of these drugs on pancreatic and thyroid tissue, since animal studies and analyses of drug databases indicate an association of GLP-1 receptor agonists with pancreatitis, pancreatic cancer, and thyroid cancer. However, several meta-analyses failed to confirm a cause-effect relation between GLP-1 receptor agonists and the development of these adverse effects. One benefit of GLP-1 receptor agonists is that they do not cause hypoglycemia when combined with metformin or thiazolidinediones, but the dose of concomitant sulphonylurea or insulin may have to be decreased to reduce the risk of hypoglycemic episodes. On the other hand, several case reports have linked the use of these drugs, mainly exenatide, with the occurrence of acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea. The most common symptoms associated with the use of GLP-1 receptor agonists are gastrointestinal symptoms, mainly nausea. Other common adverse effects include injection site reactions, headache, and nasopharyngitis, but these effects do not usually result in discontinuation of the drug. Current evidence shows that GLP-1 receptor agonists have no negative effects on the cardiovascular risk of patients with T2D. Thus, GLP-1 receptor agonists appear to have a favorable safety profile, but ongoing trials will further assess their cardiovascular effects. The aim of this review is to analyze critically the available data regarding adverse events of GLP-1 receptor agonists in different anatomic systems published in Pubmed and Scopus. Whenever possible, certain differences between GLP-1 receptor agonists are described. The review also provides the reader with structured data that compare the rates of the most common adverse effects for each of the various GLP-1 receptor agonists.

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“…There was a reduction of daily insulin dose of 42 + 2 Units (mean + SE) from a baseline of 120 + 99 Units (mean + SD), and 16.6% of patients discontinued insulin. 15 Herein we have assessed even more specific subgroups of patients in the audits; noting the glycaemic efficacy of exenatide and liraglutide as add-on therapies to one or two OADs as compared with add-on therapy to basal insulin (± OAD) or biphasic insulin (± OAD) at six months of treatment. Data have been adjusted for baseline HbA1c.…”

Section: The Use Of Exenatide or Liraglutide With Insulinmentioning

confidence: 99%

GLP-1 receptor agonists in type 2 diabetes - NICE guidelines versus clinical practice

et al. 2014

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Injectable glucagon-like peptide-1 receptor agonists (GLP1ras) have the distinct advantage of promoting weight loss as well as lowering glucose in type 2 diabetes. Treatment with a GLP-1ra is costly, thereby necessitating a restriction on widespread use, thus in the UK the National Institute for Health and Care Excellence (NICE) has published guidance on the use of these drugs.In the UK the Association of British Clinical Diabetologists (ABCD) conducted two nationwide audits on the use of exenatide twice daily and liraglutide once daily and noticed that deviations from NICE guidelines were common. Herein data have been used from both audits (following a combined total of 12,955 type 2 diabetes patients) to evaluate these treatment decisions, critically appraise the NICE guidelines and formulate recommendations for the use of GLP-1ras. Br J Diabetes Vasc Dis 2014;14:52-59

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Safety, efficacy and tolerability of exenatide in combination with insulin in the Association of British Clinical Diabetologists nationwide exenatide audit*

Cited by 85 publications

References 23 publications

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)

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)

Adverse Effects of GLP-1 Receptor Agonists

GLP-1 receptor agonists in type 2 diabetes - NICE guidelines versus clinical practice

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