Effects of lixisenatide on postprandial blood pressure, gastric emptying and glycaemia in healthy people and people with type 2 diabetes

Diabetes Obes Metab. 2019 May;21(5):1158-1167. doi: 10.1111/dom.13633. Epub 2019 Feb 14.

Abstract

Aim: To evaluate the effects of the prandial glucagon-like peptide-1 receptor agonist lixisenatide on gastric emptying and blood pressure (BP) and superior mesenteric artery (SMA) blood flow, and the glycaemic responses to a 75-g oral glucose load in healthy people and those with type 2 diabetes (T2DM).

Materials and methods: Fifteen healthy participants (nine men, six women; mean ± SEM age 67.2 ± 2.3 years) and 15 participants with T2DM (nine men, six women; mean ± SEM age 61.9 ± 2.3 years) underwent measurement of gastric emptying, BP, SMA flow and plasma glucose 180 minutes after a radiolabelled 75-g glucose drink on two separate days. All participants received lixisenatide (10 μg subcutaneously) or placebo in a randomized, double-blind, crossover fashion 30 minutes before the glucose drink.

Results: Lixisenatide slowed gastric emptying (retention at 120 minutes, P < 0.01), attenuated the rise in SMA flow (P < 0.01) and markedly attenuated the decrease in systolic BP (area under the curve [AUC] 0-120 minutes, P < 0.001) compared to placebo in healthy participants and those with T2DM. Plasma glucose (incremental AUC 0-120 minutes) was greater in participants with T2DM (P < 0.005) than in healthy participants, and lower after lixisenatide in both groups (P < 0.001).

Conclusions: In healthy participants and those with T2DM, the marked slowing of gastric emptying of glucose induced by lixisenatide was associated with attenuation of the increments in glycaemia and SMA flow and decrease in systolic BP. Accordingly, lixisenatide may be useful in the management of postprandial hypotension.

Keywords: blood pressure; gastric emptying; lixisenatide; postprandial hypotension; type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Double-Blind Method
  • Female
  • Gastric Emptying / drug effects*
  • Healthy Volunteers
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Humans
  • Male
  • Middle Aged
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Placebos
  • Postprandial Period / drug effects*

Substances

  • Blood Glucose
  • Peptides
  • Placebos
  • lixisenatide