Clinical trial NCT02042664: Effect of GLP-1 Receptor (GLP-1R) Agonists on Cardiac Function and on Epicardial Adipose Tissue (EAT) Volume and on Myocardial TG Content in Obese Diabetics
Official title: Effect of GLP-1 Receptor (GLP-1R) Agonists on Cardiac Function and on Epicardial Adipose Tissue (EAT) Volume and on Myocardial TG Content in Obese Diabetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Obesity
Diabetes
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2014-01-23
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Glucagon-like peptide-1 (GLP-1) receptor agonist are new treatment of type 2 diabetes, they lower blood glucose level (by enhancement of glucose-dependent insulin secretion and suppression of excess glucagon secretion) and reduce weight by inducing satiety and slowing of gastric emptying. Beneficial effects of GLP-1 and GLP-1 receptor (GLP-1R) agonists on cardiovascular function have been suggested. They improve biomarkers of CV risk, decrease systolic blood pressure, improve endothelial function and have beneficial effects on myocardium. Nevertheless, few studies have analysed the effect of GLP1 treatment on myocardial function in type 2 obese diabetic.

Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. It was recently shown that 16 weeks of caloric restriction in obese patients with diabetes decrease myocardial triglyceride content and improve myocardial function (cardiac output, normalized stroke volume, LV mass and normalized end diastolic volume), and diastolic function. However, no study has evaluated the impact of Glucagon-like peptide-1 (GLP-1) receptor agonist in obese diabetics on myocardial TG content.

Recent studies have suggested that increased epicardial adipose tissue (EAT) could be an important risk factor for cardiac diseases. We and others have already evidenced a correlation between the volume of epicardial adipose tissue and the presence or the severity of coronaropathy. The impact of weight loss on the volume of EAT or the characteristics of EAT is mostly unknown.


Eligibility criteria: Inclusion Criteria:

* - Patients with type 2 diabetes according to WHO criteria
* Age\> 18 years
* BMI ≥ 30 kg/m2
* HbA1c\> 7% and \<10%
* Processing by ADO (Metformin and Glimepiride)
* Effective contraception (for women)
* Signed informed consent by the patient before inclusion in the protocol

Exclusion Criteria:

* Ongoing pregnancy or become pregnant within six months of the study protocol
* Breastfeeding
* Recent weight loss (\> 5% of total weight)
* Treatments changing the distribution of adipose tissue as corticosteroids or glitazones
* Acute coronary syndrome or unstable angina during the last three months
* Contraindications to cardiac MRI (mechanical heart valve, pacemaker, metallic intraocular foreign body, claustrophobia)
* Contraindication to cold test: Raynaud's syndrome
* Contraindication to exenatide:

  * Neoplasia active or untreated or in remission for less than 5 years (except for basal cell carcinoma or in situ cervical or prostate)
  * Contraindication to ADO (depending on specific product) in combination with exenatide.
  * History of kidney transplant or dialysis or plasmatique creatinine\> 1.5 mg / dL for men and\> 1.2 mg / dL for women
  * Digestive diseases, including gastroparesis
  * plasma triglycerides\> 1000 mg / dL
  * History of pancreatitis confirmed biologically
  * contraindication or hypersensitivity to Exenatide or one of its social coverage composantsAbsence

Primary outcomes:
measure: intracardiac triglyceride
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Marseille
country: France
facility: Assistance Publique Hopitaux de Marseille
Study officials:
affiliation: Assistance Publique Hopitaux De Marseille
name: LOIC modoloni
role: STUDY_DIRECTOR
References: