Lixisenatide reduces postprandial hyperglycaemia via gastrostatic and insulinotropic effects

Diabetes/metabolism Research and Reviews
Reinhard H A BeckerFranck Pellissier

Abstract

Lixisenatide is a once-daily, prandial, short-acting glucagon-like peptide-1 receptor agonist. Its main antidiabetic effect is to delay gastric emptying to control postprandial plasma glucose excursions. The dose-response relationship of the integrated insulinotropic and gastrostatic response to lixisenatide in healthy volunteers after a standardized liquid meal was investigated. Twenty healthy subjects received acetaminophen 1000 mg with a standardized liquid meal 60 min after a single subcutaneous injection of placebo or lixisenatide 2.5, 5, 10 or 20 µg in randomized order separated by a 2- to 7-day washout. Acetaminophen pharmacokinetics served as a surrogate to assess rate of gastric emptying. Postprandial plasma glucose, insulin, C-peptide and glucagon were assessed for 5 h after the meal test, and lixisenatide pharmacokinetics were determined for 6 h. After lixisenatide administration and prior to the standardized meal, insulin and C-peptide transiently increased, while fasting plasma glucose decreased in a dose-dependent manner. After the meal, postprandial plasma glucose, insulin and C-peptide were dose proportionally reduced with lixisenatide versus placebo for up to 6 h. Compared with placebo, glucagon levels were tra...Continue Reading

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Oct 22, 2016·Diabetes, Obesity & Metabolism·Lawrence BlondeRonald M Goldenberg
Nov 4, 2016·Expert Opinion on Drug Metabolism & Toxicology·Markolf HanefeldLouis Monnier
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Oct 18, 2020·Molecular Metabolism·Michael A NauckJuris J Meier

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