Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial

Garber, Alan J.; Henry, Robert R.; Ratner, Robert E.; García-Hernández, Pedro Alberto; Rodriguez-Pattzi, Hiromi; Olvera-Alvarez, I.; Hale, Paula M; Zdravković, Milan; Bode, Bruce W.

doi:10.1016/s0140-6736(08)61246-5

Cited by 934 publications

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“…Interestingly, the amount of insulin-induced weight gain was not significantly related to the amount of liraglutide-induced weight loss. In contrast with the registration trials [10][11][12][13][14], weight loss with liraglutide was inversely related to BMI, with the greatest weight loss occurring in patients with a lower rather than a higher BMI.…”

Section: Discussionmentioning

confidence: 58%

“…Glucagon-like peptide-1 (GLP-1) analogues stimulate insulin secretion, suppress glucagon release, and reduce food intake, resulting in improved glycaemic control and weight loss in type 2 diabetes [9][10][11][12][13][14][15]. Addition of GLP-1 analogues to insulin therapy may thus be beneficial in reversing pronounced insulin-induced weight gain.…”

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: 58%

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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“…21,22 Most of the pre-registration studies also excluded patients with BMI > 45 kg/m 2 . [23][24][25][26][27][28] Hence, the BMI restriction of >35 kg/m 2 adopted by NICE is not strictly evidenced-based.…”

Section: Commentmentioning

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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“…Liraglutide is 97% homologous to human GLP-1, with only a single amino acid substitution and a glutamate-spaced fatty acid chain to distinguish it from the native peptide [105]. These modifications slow the degradation of liraglutide by DPP-4, thereby extending plasma half-life to 13 h [106][107][108][109].Liraglutide produces clinically meaningful reductions in HbA1c and body weight relative to placebo [91,92,[110][111][112]. In a double-blind, placebocontrolled, 52-week study evaluating the effects of liraglutide or glimepiride as first-line monotherapy in 746 people with type 2 diabetes, body weight was reduced by 2.05 ± 4.40 and 2.45 ± 4.37 kg in the liraglutide 1.2 and 1.8 mg cohorts respectively, compared with weight gain of 1.12 ± 4.24 kg in those receiving glimepiride 8 mg (p < 0.0001 for both vs. glimepiride).…”

mentioning

confidence: 99%

Diabesity: therapeutic options

Colagiuri¹

2010

Diabetes Obesity Metabolism

102

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A pathogenic relationship exists between type 2 diabetes and obesity. Over the last decade, the escalation in diabetes cases has paralleled the rapid increase in obesity rates, constituting a global health crisis. Environmental risk factors attributed to the global increase in obesity include the consumption of high-calorie, high-fat foods and inadequate physical activity. Obese individuals may also have a genetic predisposition for obesity. Both diabetes and obesity confer an elevated risk of developing a range of complications and comorbidities, including cardiovascular disease, hypertension and stroke, which can complicate disease management. This review examines the aetiology of the linkages between diabetes and obesity and the range of available therapies. Recent clinical evidence substantiating the efficacy and safety of incretin-based antidiabetic therapies is analysed, in addition to data on antiobesity therapeutic strategies, such as antiobesity agents, behaviour modification and bariatric surgery. Glucose control is often accompanied by weight-neutral or modest weight reduction effects with DPP-4 inhibitor treatment (sitagliptin, vildagliptin, saxagliptin) and weight loss with GLP-1 receptor agonist therapy (exenatide, liraglutide). Studies of antiobesity agents including orlistat, sibutramine and rimonabant have shown attrition rates of 30-40%, and the long-term effects of these agents remain unknown. Bariatric surgical procedures commonly performed are laparoscopic adjustable banding of the stomach and the Roux-en-Y gastric bypass, and have produced type 2 diabetes remission rates of up to 73%. Therapeutic strategies that integrate glycaemic control and weight loss will assume greater importance as the prevalence of diabetes and obesity increase. Keywords: DPP-4, exenatide, GLP-1 analogue, human, incretin, liraglutide, once-daily, type 2 diabetes mellitus Date submitted 2 June 2009; date of first decision 2 November 2009; date of final acceptance 4 November 2009 IntroductionThe term 'diabesity', coined by Sims and colleagues [1] in the 1970s, describes the strong link between type 2 diabetes and obesity [1,2]. As evidence of this pathogenic interrelationship continues to accumulate, so does the appearance of the term in the clinical literature. A large body of clinical evidence attests to the relationship between being overweight or obese and being at an elevated risk for development of type 2 diabetes [3][4][5][6][7]. The risk escalates with the degree of excess weight, increasing threefold with a body mass index (BMI) of 25.0-29.9 kg/m 2 and 20-fold with a BMI over 30 kg/m 2 [4]. In particular, abdominal fat accumulation exacerbates insulin resistance and confers a strong, independent risk of developing diabetes [8]. Global diabetes prevalence is estimated at 171 million and is projected to more than double, to 366 million, by 2030 [9]. Countries with the highest numbers of diabetes cases include India, China, USA, Indonesia and Japan [9][10][11]. The greatest relative increases in diabetes incide...

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Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial

Cited by 934 publications

References 14 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)

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

Diabesity: therapeutic options

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