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

ABSTRACT 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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    • " 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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    • "Gut hormones play essential roles in a wide range of metabolic functions such as the regulation of food absorption, appetite, and glucose homeostasis . As a consequence, drugs that enhance GLP-1 action are now widely used in the treatment of T2DM (Garber et al., 2009; Nauck et al., 2009; Zinman et al., 2009) and are under investigation for the treatment of obesity (Marre et al., 2009). Attention is also turning toward the enteroendocrine L cells themselves and whether they could be targeted for the treatment of obesity and diabetes. "
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    • "A meta-analysis of GLP-1 receptor agonists in type 2 diabetes and obesity, including eight trials using liraglutide, also demonstrated a positive effect on weight loss (17). In type 2 diabetes, mean weight losses of 2.05, 2.45, and 2.8 kg after 52 weeks of liraglutide 1.2, 1.8, and 26 weeks of liraglutide 1.8 mg in combination with metformin, respectively, have been reported (16, 21, 22). In obese non-diabetic subjects, liraglutide in doses of 1.2, 1.8, 2.4, and 3.0 mg resulted in mean weight losses of 4.8, 5.5, 6.3, and 7.2 kg, respectively, after 20 weeks (23). "
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