Differential effects of GLP-1 receptor agonists on components of dysglycaemia in individuals with type 2 diabetes mellitus

Oct 26, 2013Diabetes & metabolism

Different effects of GLP-1 medicines on blood sugar problems in people with type 2 diabetes

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Abstract

Long-acting GLP-1 receptor agonists show greater reductions in fasting plasma glucose compared to shorter-acting formulations.

GLP-1 receptor agonists improve glucose metabolism by enhancing insulin secretion and reducing glucagon release.
Differences in drug characteristics lead to varying effects on fasting and post-prandial glucose levels.
Liraglutide once daily and exenatide once weekly significantly lower fasting plasma glucose but have less impact on post-prandial glucose spikes.
Shorter-acting prandial GLP-1 receptor agonists like exenatide twice daily effectively manage post-prandial glucose through delayed gastric emptying.
Lixisenatide once daily strongly suppresses post-prandial glucagon secretion, enhancing its glucose-lowering effects.
Prandial GLP-1 receptor agonists may be best utilized in combination with basal insulin for optimal management of type 2 diabetes mellitus.

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Metabolic consequences of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are the result of enhanced glucose-stimulated insulin secretion, inhibition of glucagon release, delayed gastric emptying and increased satiety. These attributes make GLP-1 agonists a treatment option in type 2 diabetes mellitus (T2DM). To optimise treatment choice, a detailed understanding of the effects of GLP-1 RAs on glucose homeostasis in individuals with T2DM is necessary. Although the various GLP-1 RAs share the same basic mechanisms of action, differences in pharmacokinetic/pharmacodynamic characteristics translate into differential effects on parameters of glycaemia. Head-to-head comparisons between long-acting non-prandial (liraglutide once daily and exenatide once weekly) and shorter-acting prandial (exenatide twice daily and lixisenatide once daily prandial) GLP-1 RAs confirm their differential effects on fasting plasma glucose (FPG) and post-prandial glucose (PPG). Liraglutide once daily and exenatide once weekly demonstrate greater reductions in FPG but lesser impacts on PPG excursions plasma than exenatide twice daily. Prandial GLP-1 RAs have a profound effect on post-prandial glycaemia, mediated by delaying gastric emptying, which is not subject to the tachyphylaxis occurring due to the sustained elevated plasma GLP-1 concentrations after treatment with long-acting GLP-1 RAs. Lixisenatide once-daily prandial, in contrast to liraglutide, strongly suppresses post-prandial glucagon secretion, further contributing to the more pronounced PPG-lowering effect found with lixisenatide. Evidence suggests that the GLP-1 RAs that predominantly target the prandial glucose excursions, such as exenatide twice daily and lixisenatide once-daily prandial, are therefore best used as combination therapy with basal insulin and will form an important new treatment option for individuals with T2DM.

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Differential effects of GLP-1 receptor agonists on components of dysglycaemia in individuals with type 2 diabetes mellitus

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