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

Baylor College of Medicine, Houston, TX, USA.
The Lancet (Impact Factor: 45.22). 10/2008; 373(9662):473-81. DOI: 10.1016/S0140-6736(08)61246-5
Source: PubMed


New treatments for type 2 diabetes mellitus are needed to retain insulin-glucose coupling and lower the risk of weight gain and hypoglycaemia. We aimed to investigate the safety and efficacy of liraglutide as monotherapy for this disorder.
In a double-blind, double-dummy, active-control, parallel-group study, 746 patients with early type 2 diabetes were randomly assigned to once daily liraglutide (1.2 mg [n=251] or 1.8 mg [n=247]) or glimepiride 8 mg (n=248) for 52 weeks. The primary outcome was change in proportion of glycosylated haemoglobin (HbA(1c)). Analysis was done by intention-to-treat. This trial is registered with, number NTC00294723.
At 52 weeks, HbA(1c) decreased by 0.51% (SD 1.20%) with glimepiride, compared with 0.84% (1.23%) with liraglutide 1.2 mg (difference -0.33%; 95% CI -0.53 to -0.13, p=0.0014) and 1.14% (1.24%) with liraglutide 1.8 mg (-0.62; -0.83 to -0.42, p<0.0001). Five patients in the liraglutide 1.2 mg, and one in 1.8 mg groups discontinued treatment because of vomiting, whereas none in the glimepiride group did so.
Liraglutide is safe and effective as initial pharmacological therapy for type 2 diabetes mellitus and leads to greater reductions in HbA(1c), weight, hypoglycaemia, and blood pressure than does glimepiride.

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    • "Three dosages of liraglutide, 0.6 mg daily, 1.2 mg daily and 1.8 mg daily, were compared with active comparator or placebo for efficacy and safety assessments. The active comparators were insulin glargine (Russell-Jones et al., 2009), glimepiride (sulfonylurea) (Garber et al., 2009), exenatide (GLP-1 receptor agonist) (Buse et al., 2009), rosiglitazone (glitazone) (Marre et al., 2009) and sitagliptin (DPP-4 inhibitor) (Pratley et al., 2012). In the LEAD studies including a placebo arm, placebo-treated patients also received background oral antidiabetic drug therapy. "
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    • " remains in circulation ( Knudsen et al . , 2000 ) . The half - life for liraglutide is about 10 – 14 h in humans ( Agerso et al . , 2002 ) and is recommended for once - daily administration . Both exenatide ( DeFronzo et al . , 2005 ; Heine et al . , 2005 ; Moretto et al . , 2008 ; Norris et al . , 2009 ) and liraglutide ( Astrup et al . , 2009 ; Garber et al . , 2009 ; Niswender et al . , 2013 ; Lean et al . , 2014 ) significantly improve glycemic control and cause a significant body weight loss in T2DM patients . Gastrointestinal side effects including nau - sea and vomiting have been reported with both exenatide and liraglutide treatment although these side effects are often tran - sient and occur"
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