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
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 ClinicalTrials.gov, 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.
- SourceAvailable from: Kristy Heppner
[Show abstract] [Hide abstract]
- " 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"
ABSTRACT: Glucagon-like peptide-1 (GLP-1) enhances meal-related insulin secretion, which lowers blood glucose excursions. In addition to its incretin action, GLP-1 acts on the GLP-1 receptor (GLP-1R) in the brain to suppress feeding. These combined actions of GLP-1R signaling cause improvements in glycemic control as well as weight loss in type II diabetes (T2DM) patients treated with GLP-1R agonists. This is a superior advantage of GLP-1R pharmaceuticals as many other drugs used to treat T2DM are weight neutral or actual cause weight gain. This review summarizes GLP-1R action on energy and glucose metabolism, the effectiveness of current GLP-1R agonists on weight loss in T2DM patients, as well as GLP-1R combination therapies.Frontiers in Neuroscience 03/2015; 9:92. DOI:10.3389/fnins.2015.00092 · 3.70 Impact Factor
[Show abstract] [Hide abstract]
- "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. "
ABSTRACT: It has long been speculated that metabolites, produced by gut microbiota, influence host metabolism in health and diseases. Here, we reveal that indole, a metabolite produced from the dissimilation of tryptophan, is able to modulate the secretion of glucagon-like peptide-1 (GLP-1) from immortalized and primary mouse colonic L cells. Indole increased GLP-1 release during short exposures, but it reduced secretion over longer periods. These effects were attributed to the ability of indole to affect two key molecular mechanisms in L cells. On the one hand, indole inhibited voltage-gated K+ channels, increased the temporal width of action potentials fired by L cells, and led to enhanced Ca2+ entry, thereby acutely stimulating GLP-1 secretion. On the other hand, indole slowed ATP production by blocking NADH dehydrogenase, thus leading to a prolonged reduction of GLP-1 secretion. Our results identify indole as a signaling molecule by which gut microbiota communicate with L cells and influence host metabolismCell Reports 11/2014; 9(4). DOI:10.1016/j.celrep.2014.10.032 · 8.36 Impact Factor
[Show abstract] [Hide abstract]
- "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). "
ABSTRACT: Objective: The aim of the present study was to evaluate the effect of the glucagon-like peptide-1 analog liraglutide on weight loss in overweight and obese women with polycystic ovary syndrome (PCOS). Methods: In an observational study, 84 overweight or obese women with PCOS were treated with liraglutide. Baseline characteristics and weight changes at clinical follow-up were recorded. Main outcome measures were absolute and relative weight loss. Results: In overweight or obese women with PCOS treated with liraglutide for a minimum of 4 weeks, a mean weight loss of 9.0 kg (95% CI: 7.8–10.1, p < 0.0001) and a mean decrease in BMI of 3.2 kg/m2 (95% CI: 2.8–3.6, p < 0.0001) were found. A weight loss of more than 5 and 10% of baseline weight was seen in 81.7 and 32.9% of patients, respectively. The mean duration of treatment with liraglutide was 27.8 weeks (SD 19.2). Conclusion: Treatment with liraglutide in combination with metformin and lifestyle intervention resulted in a significant weight loss in overweight and obese women with PCOS, indicating that liraglutide may be an effective alternative for weight loss in this group of patients. However, larger placebo-controlled studies are needed to confirm this.Frontiers in Endocrinology 08/2014; 5:140. DOI:10.3389/fendo.2014.00140