Lixisenatide-The Effects on Glucose and Lipid Metabolism in Type 2 Diabetes

Status

Completed

Phase

Phase 4

Enrollment

8 participants (actual)

Sponsor

University of Surrey · Other

Design

Randomized · Quadruple masking

Countries

1 country

United Kingdom

Start

Jan 2014

Primary completion

Jan 2016

Completion

Jan 2016

First posted

29 Jan 2014 (estimated)

Last update posted

16 Dec 2024

Conditions

Type 2 Diabetes

Glucagon-like-peptide-1 (GLP-1) analogues are a new treatment for type 2 diabetes, which have recently been shown to have beneficial effects on weight, glycaemic control and postprandial triglyceride concentrations. Postprandial hypertriglyceridaemia, which is associated with an increased risk of cardiovascular disease, is a feature of type 2 diabetes. Hypertriglyceridaemia is due to excess triglyceride-rich lipoproteins (TRL) which consist of very low-density lipoproteins, (VLDL) synthesised by the liver which contain the higher molecular weight form of apolipoproteinB (apoB), apoB-100, and chylomicrons which are synthesised in the intestine in response to an intake of dietary fat and contain the lower molecular weight form of apoB, apoB-48. A recent study has shown that GLP-1 receptor signalling is required for the control of postprandial lipoprotein synthesis and secretion in hamsters and mice. GLP-1 was shown to reduce apoB-48 TRL production while a GLP-1 receptor antagonist increased apoB-48 TRL production. This study will investigate the effect of the GLP-1 analogue lixisenatide compared with placebo, in a double blind crossover study, on postprandial triglyceride metabolism in 12 patients with type 2 diabetes. Chylomicron and VLDL production and clearance rates will be measured in a repeated meal study by labelling apoB-100 and apoB-48 and by labelling triglycerides using stable isotope methodology. Glucose flux in response to a mixed fluid meal will also be investigated using stable isotope methodology. Gastric emptying and post heparin LPL activity will be measured. The hypothesis is that i\] lixisenatide will lower postprandial glycaemia due to a decrease in endogenous glucose output and an increase in glucose clearance by peripheral tissues as a result of an improvement in insulin sensitivity.

• Placebo comparator

  Placebo

  Placebo for lixisenatide is supplied as green and purple colored disposable pen-injectors containing 3 mL of a sterile aqueous solution.

• Experimental

  Lixisenatide

  Lixisenatide and placebo are considered as investigational medicinal product (IMP). Metformin is not considered an investigational product but concomitant allowed antidiabetic medications. Lixisenatide is supplied as disposable pre-filled pen for subcutaneous injection: 10mcg Lixisenatide green pens; 20 mcg Lixisenatide purple pens. Dose titration-10mcg Lixisenatide for 14 days, 20 mcg for 14 days.

1. Postprandial glucose kinetics

   Time frame · Two years

   Registry description

   The study is a double blind cross over study comparing placebo injection with lixisenatide injection. The results will not be known until the investigator is unblinded. An intravenous infusion of \[6,6 2H2\] glucose will enable the quantification of endogenous hepatic glucose output while addition of \[U13C\] glucose to a mixed meal will enable the calculation of the contribution of meal derived glucose to postprandial glucose. Enrichment of plasma samples with 2H2 glucose and 13C glucose will be measured by gas chromatography mass spectroscopy (GCMS). Glucose uptake during the postprandial period will then be determined from these measures of glucose output and the glucose concentration at each time point. During this study, gastric emptying will be measured by oral administration of 1000mg acetaminophen.