The Microvascular Function of GLP-1 and Its Analogues

Not Applicable

Completed

• Conditions: Type 2 Diabetes; Obesity
• Interventions: Drug: GLP-1; Drug: Placebo

• Registration Number: NCT01677104
• Lead Sponsor: Katarina Kos

Brief Summary

Incretins have become a successful drug target in the repertoire of medications used for the treatment of type 2 diabetes. However little is known about a potential benefit of GLP-1 on the vascular system in humans, independent of their glucose lowering actions and data are only derived from ex vivo studies in animals. Particularly little is known about clinically relevant benefits of GLP-1 and its analogues on the microvascular system of individuals with type 2 diabetes.

The vascular effect could be medicated by endogenous GLP-1 (9,36) amide, the breakdown product of GLP-1 (7,36) amide which has a low affinity for the GLP-1 receptor. The investigators hypothesis is that the co-administration of DPP-IV inhibitors will lack the beneficial effects of GLP-1 on the vascular system as GLP-1 (9,36) amide will not be produced by the body.

The study aims to examine the response of GLP-1 and its analogues on small blood vessels and examine the effect of the addition of DPP-IV inhibition in healthy lean individuals, obese individuals and subjects with Type 2 diabetes.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-08
• Study First Submitted: 2012-08-29
• Study First Submitted QC: 2012-08-30
• Study First Posted: 2012-08-31
• Primary Completion: 2014-07
• Study Completion: 2014-07
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-12
• Last Update Posted: 2017-04-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

• Lean BMI ≤ 25.0 kg/m2
• Obese BMI ≥30.0kg/m2
• Non diabetic subjects and subjects with Type 2 diabetes on stable medication for at least 3 months

Exclusion Criteria

• cardiovascular disease
• Raynaud's disease
• current treatment with any anti-hypertensive
• lipid lowering therapies
• severe hepatic impairment
• pregnancy and lactation
• subjects with Type 2 diabetes on insulin therapy
• subjects with Type 2 diabetes on sulphonylureas
• subjects with Type 2 diabetes on incretin based therapies
• subjects with Type 2 diabetes and peripheral vascular disease
• subjects with Type 2 diabetes and history of advanced retinopathy
• subjects with Type 2 diabetes and advanced nephropathy
• subjects with Type 2 diabetes with uncontrolled diabetes (HbA1c > 8.5%)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
DPP-IV inhibitor	GLP-1	Linagliptin 5mg (Tradjenta) before microinjection of GLP-1 and its analogues
DPP-IV inhibitor	Placebo	Linagliptin 5mg (Tradjenta) before microinjection of GLP-1 and its analogues
Placebo pill	GLP-1	One placebo tablet before microinjection
Placebo pill	Placebo	One placebo tablet before microinjection

Primary Outcome Measures

Name	Time	Method
skin blood flow	3 hours	skin blood flow will be assessed before and after microinjection of GLP-1 or its analogues and the injection site monitored and compared to sites injected with placebo

Trial Locations

Locations (1)

Diabetes and Vascular Center; 🇬🇧 Exeter, United Kingdom