Effects of the GLP-1 receptor agonist lixisenatide on postprandial glucose and gastric emptying – preclinical evidence

Sep 3, 2013Journal of diabetes and its complications

Lixisenatide’s effects on blood sugar and stomach emptying after meals in preclinical studies

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Abstract

Lixisenatide is associated with reduced postprandial glucose excursions and delayed gastric emptying.

Glucagon-like peptide 1 (GLP-1) influences appetite and body weight regulation.
Short-acting GLP-1 receptor agonists primarily target postprandial glucose control.
Lixisenatide, a short-acting GLP-1 receptor agonist, is administered once daily.
Preclinical studies indicate that lixisenatide effectively reduces postprandial glucose levels.
The delay in gastric emptying from lixisenatide does not show tachyphylaxis, unlike long-acting agents.

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In addition to promoting glucose homeostasis, glucagon-like peptide 1 (GLP-1) has a number of extra-pancreatic effects that regulate appetite and body weight. GLP-1 delays gastric emptying, which is vital for postprandial glucose (PPG) control. As GLP-1 is rapidly degraded by protease dipeptidyl peptidase-4, a number of degradation-resistant GLP-1 receptor agonists (GLP-1RAs) have been developed for the treatment of Type 2 diabetes mellitus. These agents can be broadly categorized as being short- or long-acting, based on their pharmacokinetic profile. Short-acting agonists predominantly affect PPG and delay gastric emptying in a sustained manner, whereas long-acting agents largely affect fasting plasma glucose and their delay in gastric emptying appears to be subjected to tachyphylaxis. Lixisenatide is a "short-acting" once-daily prandial GLP-1RA. This review provides an overview of the preclinical studies that are currently available and that evaluate the efficacy of lixisenatide on gastric emptying and PPG levels. The preclinical evidence outlined in this review supports the efficacy of lixisenatide in reducing PPG excursions and delaying gastric emptying. Furthermore, in contrast to long-acting agents, the actions of lixisenatide do not appear to be subjected to tachyphylaxis.

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Effects of the GLP-1 receptor agonist lixisenatide on postprandial glucose and gastric emptying – preclinical evidence

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