The Vascular Effects of Vildagliptin in Insulin Resistant Individuals
Animal models have demonstrated that incretins have a glucose-independent effect on vascular perfusion, and there is limited evidence that incretins may enhance endothelial function in healthy subjects. Currently DPP-4 inhibition increases levels of the endogenous incretin Glucagon-like Peptide 1 (GLP-1) and is licensed for the treatment of hyperglycaemia in type 2 diabetes. They are positioned as third or even fourth line therapy after metformin, sulphonylureas ± glitazones, however recent analyses of cardiovascular outcomes in glitazones and sulphonylureas suggest at best they do not reduce cardiovascular endpoints, and may increase some outcomes. If the vascular benefits suggested in animal models are realised in humans this should see the DPP-4 inhibitors moved to second line and possibly 1st line.
In order to realise the potential the investigators would like initially to demonstrate increases in vascular perfusion and function in a placebo controlled trial using accurate surrogates for vascular function in patients with insulin resistance and obesity.
The investigators hypothesis is that by increasing incretin activity in insulin resistant states the investigators will lower capillary pressure and improve microvascular function, which will be accompanied by a reduction in macular thickness (by reducing macular oedema) and microalbuminuria, recognised surrogates for early diabetic retinopathy and renal failure respectively.
|Insulin Resistance Microvascular Disease||Drug: Vildagliptin Drug: Placebo||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Does Modulating the Gut Hormones, Incretins, Modify Vascular Function, Thereby Reducing the Risk of Vascular Complications in Insulin Resistant Individuals?|
- Capillary pressure [ Time Frame: 3 months ]Capillary pressure will be reduced in those treated with DPP-4 inhibitor
- Macular thickness [ Time Frame: 3 months ]Measured by optical coherence tomography
|Study Start Date:||May 2010|
|Study Completion Date:||August 1, 2014|
|Primary Completion Date:||August 1, 2014 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Placebo||
Vildagliptin 50mg bid
Vildagliptin 50mg bid
Other Name: Galvus
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01122641
|Diabetes and Vascular Research Department|
|Exeter, Devon, United Kingdom, EX2 5AX|