Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)

Buse, John B.; Rosenstock, Julio; Sesti, Giorgio; Schmidt, Wolfgang E.; Montanya, Eduard; Brett, Jason; Zychma, Marcin; Blonde, Lawrence

doi:10.1016/s0140-6736(09)60659-0

Cited by 1,339 publications

(1,742 citation statements)

References 21 publications

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“…Within the GLP-1 receptor agonist group, the longer acting agonists seem more potent, as verified by head-to-head studies showing a larger reduction in HbA 1c by liraglutide than by exenatide [40] and by once weakly exenatide versus twice daily exenatide [15]. In regard to DPP-4 inhibitors, they seem all to have similar efficacy, which is supported by a head-to-head studies comparing sitagliptin with saxagliptin as add-on to metformin.…”

Section: Comparisons Between Glp-1 Receptor Agonists and Dpp-4 Inhibimentioning

confidence: 78%

GLP-1 for type 2 diabetes

Åhrén

2011

Experimental Cell Research

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Glucagon-like peptide-1 (GLP-1)-based therapy of type 2 diabetes is executed either by GLP-1 receptor agonists, which stimulate the GLP-1 receptors, or by dipeptidyl peptidase-4 (DPP-4) inhibitors, which prevent the inactivation of endogenous GLP-1 thereby increasing the concentration of endogenous active GLP-1. GLP-1 activates pancreatic receptors resulting in improved glycemia through glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion. There is also a potential beta cell preservation effect, as judged from rodent studies. GLP-1 receptors are additionally expressed in extrapancreatic tissue, having potential for the treatment to reduce body weight and to potentially have beneficial cardio-and endothelioprotective effects. Clinical trials in subjects with type 2 diabetes have shown that in periods of 12 weeks or more, these treatments reduce HbA 1c by ≈0.8-1.1% from baseline levels of 7.7-8.5%, and they are efficient both as monotherapy and in combination therapy with metformin, sulfonylureas, thiazolidinediones or insulin. Furthermore, GLP-1 receptor agonists reduce body weight, whereas DPP-4 inhibitors are body weight neutral. The treatment is safe with very low risk for adverse events, including hypoglycaemia. GLP-1 based therapy is thus a novel and now well established therapy of type 2 diabetes, with a particular value in combination with metformin in patients who are inadequately controlled by metformin alone.

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Section: Comparisons Between Glp-1 Receptor Agonists and Dpp-4 Inhibimentioning

confidence: 78%

GLP-1 for type 2 diabetes

Åhrén

2011

Experimental Cell Research

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“…Sibutramine is a sympathomimetic medication that was available for long-term treatment, and the most recent drug to be withdrawn from the market due to a side effect of increased risk of cardiovascular events. Liraglutide is a long-acting GLP-1 analog available for the treatment of type 2 diabetes that has also shown clinically relevant weight loss following treatment in both diabetic [16] and nondiabetic obese patients [17] .…”

Section: Introductionmentioning

confidence: 99%

Effects of liraglutide and sibutramine on food intake, palatability, body weight and glucose tolerance in the gubra DIO-rats

2012

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Aim: To validate the gubra DIO-rats as a useful animal model of human obesity. Methods: The gubra diet-induced obesity (DIO) rat model was based on male Sprague-Dawley rats with ad libitum access to regular chow and a palatable diet rich in fat and sugar. To evaluate the versatility of the gubra DIO-rats as a valid model of human obesity syndrome, the efficacy of 2 weight loss compounds liraglutide and sibutramine with different mechanisms of action were examined in 7-month-old gubra DIO-rats. Liraglutide (200 µg/kg, sc) was administered bi-daily, and sibutramine (5 mg/kg, po) was administered once daily for 23 d. Results: Both the compounds effectively reduced the food intake, body weight and total fat mass as measured by nuclear magnetic resonance. Whereas the 5-HT reuptake inhibitor/5-HT receptor agonist sibutramine reduced the intake of both chow and the gubradiet, the GLP-1 analogue liraglutide predominantly reduced the intake of the highly palatable diet, indicating a shift in food preference. Sibutramine lowered the insulin sensitivity index, primarily via reductions in glucose-stimulated insulin secretion. Conclusion: This animal model responds well to 2 weight loss compounds with different mechanisms of action. Moreover, the gubra DIO-rat can be particularly useful for the testing of compounds with potential effects on diet preference.

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“…Postprandial glucagon release is reduced and postprandial insulin release is enhanced 30; however, these GLP‐1RAs are less available during fasting states and are therefore less effective for reducing fasting measures. In contrast, for the long‐acting GLP‐1RAs exenatide once weekly, liraglutide, albiglutide and dulaglutide, effects on gastric emptying are not as strong as their short‐acting counterparts 31 or decline over time 32, probably as a result of the continuous GLP‐1RA exposure causing tachyphylaxis 33, leading to less pronounced PPG reductions 34. Instead, these agents appear to reduce HbA 1c concentration through sustained increase in fasting insulin 34, suppression of fasting glucagon 31, and subsequently lower fasting glucose levels.…”

Section: Effects Of Glp‐1ra Treatmentmentioning

confidence: 99%

Use of glucagon‐like peptide‐1 receptor agonists among individuals on basal insulin requiring treatment intensification

Trautmann¹,

Vora

2018

Diabet. Med.

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As Type 2 diabetes progresses, treatment is intensified with additional therapies in an effort to manage hyperglycaemia effectively and therefore avoid complications. When greater efficacy is required, options for injectable treatments include glucagon‐like peptide‐1 receptor agonists and insulin, which may be added on to oral glucose‐lowering treatments. Among individuals receiving long‐acting basal insulin as their first injectable treatment, ~40−60% are unable to achieve or maintain their target HbA1c goals. For these people, treatment intensification options are relatively limited and include the addition of short‐acting prandial insulin or a glucagon‐like peptide‐1 receptor agonist. Glucagon‐like peptide‐1 receptor agonists vary in their effects, with short‐ and long‐acting agents having a greater impact on postprandial and fasting hyperglycaemia, respectively. Studies comparing treatment intensification options have found both glucagon‐like peptide‐1 receptor agonists and prandial insulin to be effective in reducing HbA1c concentrations; however, recipients of glucagon‐like peptide‐1 receptor agonists lost weight and had a greater frequency of gastrointestinal adverse events, whereas those receiving prandial insulin gained weight and had a greater incidence of hypoglycaemia. In addition to the separate administration of a glucagon‐like peptide‐1 receptor agonist and basal insulin, fixed‐ratio combinations of a glucagon‐like peptide‐1 receptor agonist and basal insulin offer a single administration for both treatments but have less flexibility in dose titration than treatment with their individual components. For individuals who require treatment intensification beyond basal insulin, use of these various options allows physicians to target the individual needs of their patients for the achievement of optimal long‐term glycaemic control.

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Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)

Cited by 1,339 publications

References 21 publications

GLP-1 for type 2 diabetes

GLP-1 for type 2 diabetes

Effects of liraglutide and sibutramine on food intake, palatability, body weight and glucose tolerance in the gubra DIO-rats

Use of glucagon‐like peptide‐1 receptor agonists among individuals on basal insulin requiring treatment intensification

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