Effects on Re-endothelialisation With Bydureon Treatment in Type 2 Diabetes Subjects (Rebuild)

Karolinska Institute

Status and phase: Completed; Phase 4

Conditions: Restenosis; Diabetes; Atherosclerosis

Treatments: Drug: Metformin; Drug: Humulin kwickpen; Drug: Bydureon

Study type: Interventional

Funder types: Other

Identifiers

NCT02621489

BY2015

Details and patient eligibility

About

The aim of the study is to use Exenatide long-acting release (LAR) [Bydureon] to minimize vascular remodeling and neointima formation after Percutaneous Coronary Intervention (PCI) and to accelerate stent endothelialisation.

Full description

Exenatide LAR will be given as a once-weekly (s.c.) dose of Bydureon (2 mg) add on to Insulin in combination with Metformin. If patients are Insulin naïve (both groups) an initial dose of 10U (s.c.) at bedtime will be started, and further up-titrated to achieve a fP-glucose levels at 6 mmol/l. Standard care for post myocardial infarction will be given after PCI.

Primary objectives:

To test whether Bydureon, add on to Insulin Neutral Protamine Hagedorn (NPH) + Metformin, is superior vs. Insulin NPH + Metformin alone, in covered stent struts

Secondary objectives:

To test whether Bydureon, add on to Insulin NPH + Metformin, is superior vs. Insulin NPH + Metformin alone: in cardiac and endothelial functions

Enrollment: 38 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients eligible for PCI with application of DES, due to ACS.
2. Patients with known or newly diagnosed T2D (type 2 diabetes is diagnosed according to current WHO criteria or by the use of anti-diabetic drugs)
3. Male and female subjects 18-80 years.
4. HbA1c (accordingly to IFCC) 47 mmol/mol - 110 mmol/mol.
5. Signed informed consent form.

Exclusion criteria

1. Type 1 diabetes (autoantibody positive).
2. Any history of receiving GLP-1 analogues or dipeptidyl peptidase inhibitors within 6 months
3. Known severe heart failure, classified as NYHA 4.
4. Active myocarditis; malfunctioning artificial heart valve.
5. History of ventricular tachycardia within 3 months before study entry; second- or third-degree atrioventricular block.
6. Supine systolic blood pressure <85 mm Hg or >200 mm Hg at screening.
7. Primary renal impairment, creatinine clearance < 45 ml/min if treated with metformin.
8. Uncorrected hypokalemia or hyperkalemia (potassium <3.5 mmol/l or >5.5 mmol/l).
9. Significant anemia (Hb < 90 g/l)
10. Severe gastrointestinal disease, including gastroparesis. As judged by the Investigator.
11. Body mass index (BMI) > 45 kg/m2.
12. Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy in the previous 5 years. Patients with intraepithelial squamous cell carcinoma of the skin treated with topical 5FU and subjects with basal cell skin cancer are allowed to enter the trial.
13. Females of child bearing potential who are pregnant, breast-feeding or intend to become pregnant.
14. Current drug and alcohol abuse.
15. History of acute or chronic pancreatitis
16. Subjects considered by the Investigator to be unsuitable for the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

38 participants in 2 patient groups

Bydureon 2 mg Once Weekly

Experimental group

Description:

Patients randomised to Bydureon will be treated with Metformin 1g BID, and only receive 10U of Humulin kwickpen QD at bedtime, with no more up-titration of insulin during the study.

Treatment:

Drug: Humulin kwickpen

Drug: Bydureon

Drug: Metformin

Humulin kwickpen

Active Comparator group

Description:

Patients randomised to the comparator group will be treated with Meformin 1g BID and Humulin kwickpen to reach a fP-glucose level of 6 mmol/l. For that reason patients will be instructed to increase the bedtime Insulin dose of 2-4U every third day until this goal is reached.

Treatment:

Drug: Humulin kwickpen

Drug: Metformin