Clinical trial NCT01677104: The Microvascular Function of GLP-1 and Its Analogues
Official title: The Microvascular Function of GLP-1 and Its Analogues in Humans, in Vivo: the Role of DPP-IV Inhibition
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes
Obesity
Keywords: GLP-1
DPP-IV inhibitor
microcirculation
Exenatide
Liraglutide
Linagliptin
Lead sponsor: Royal Devon and Exeter NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Diabetes UK
First posted: 2012-08-31
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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%)

Primary outcomes:
measure: skin blood flow
timeFrame: 3 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Exeter
country: United Kingdom
facility: Diabetes and Vascular Center
Study officials:
affiliation: Institue of Biomedical and Clinical Sciences, Peninsula Medical School, University of Exeter
name: Katarina Kos, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aung MM, Slade K, Freeman LAR, Kos K, Whatmore JL, Shore AC, Gooding KM. Locally delivered GLP-1 analogues liraglutide and exenatide enhance microvascular perfusion in individuals with and without type 2 diabetes. Diabetologia. 2019 Sep;62(9):1701-1711. doi: 10.1007/s00125-019-4918-x. Epub 2019 Jun 16.