GLP-1 and Microvascular Function in Type 2 Diabetes

Not Applicable

Completed

• Conditions: Type 2 Diabetes
• Interventions: Other: diet; Drug: Aspirin; Drug: Liraglutide

• Registration Number: NCT01740921
• Lead Sponsor: Royal Devon and Exeter NHS Foundation Trust

Brief Summary

Some gut hormones, called incretins, stimulate insulin production in order to control sugar levels but also activate brain centres and signal to stop eating. Current administration of incretin-based therapies mimicking these gut hormones is by subcutaneous (just under the skin) injection and has been routinely available for diabetic patients for more than 4 years. It is an effective treatment for the lowering of blood glucose with an average weight loss of about 3-4kg.Recent evidence, from animal studies and limited human studies, suggests that incretins based treatments may also have beneficial effects on blood vessel function. However, it is not known whether this effect is by direct action on the blood vessel independent of an improvement of latent inflammation which is typically associated with weight loss or an anti-inflammatory effect of the incretin treatment itself. The aim of this study is to determine whether the incretin-based diabetes treatment with the GLP-1 (Glucagon-like peptide 1) analogue Liraglutide (also known as Victoza), which mimics the actions of incretins, improves blood vessel function in individuals with type 2 diabetes. It will determine whether the improvement in blood vessel function is independent of the effect of weight loss and changes in inflammation. This by the study of vascular function before and after 4 months of Victoza treatment in subjects with Type 2 diabetes in comparison with 1) participants randomized to hypo-caloric diet to achieve a similar weight loss than with Victoza and 2) participants randomized to treatment with once daily aspirin. Comprehensive assessment of blood vessel function, body fat distribution and metabolic profile at baseline and at the end of the treatment phase will be combined with assessments of inflammation markers in blood and in fat tissue biopsies.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01
• Study First Submitted: 2012-11-22
• Study First Submitted QC: 2012-12-03
• Study First Posted: 2012-12-04
• Primary Completion: 2015-12
• Study Completion: 2016-02
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-16
• Last Update Posted: 2017-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

• Type 2 diabetes and an HbA1C between 7-8.5% on a stable dose of sulphonylurea and/or metformin

Exclusion Criteria

• use of insulin
• corticosteroids
• contraceptives, tamoxifen
• methotrexate
• DPP-IV inhibitors
• pregnancy
• lactation
• endocrine disorders
• acute MI or cerebrovascular disease
• Raynaud's disease or connective tissue disease
• current or previous history of malignancy
• subjects treated with ergotamine derivatives
• unstable blood pressure for the last 3 months
• current treatment with warfarin
• subjects on any anti-inflammatory or anti-platelet agents
• history of any bleeding disorders and GI bleeds.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
diet	diet	reduction in calorie intake
Aspirin	Aspirin	Aspirin 300mg once daily
Liraglutide	Liraglutide	Liraglutide (Victoza) daily injections

Primary Outcome Measures

Name	Time	Method
change of baseline skin maximum hyperaemia at 4 months	baseline and 4 months	laser doppler fluximetry

Secondary Outcome Measures

Name	Time	Method
change of baseline peripheral arterial tone at 4 months	baseline and 4 months	ITAMAR
change of baseline endothelial-dependent vasodilation at 4 months	baseline and 4 months	iontophoresis
change of baseline capillary density at 4 months	baseline and 4 months	capillaroscopy

Trial Locations

Locations (1)

Peninsula Clinical Research Facility; 🇬🇧 Exeter, United Kingdom