The Effect of the GLP-1 Receptor Agonists on Blood Levels of Lipoprotein (a)

Lipoprotein (a) \[Lp (a)\] is an independent cardiovascular risk (CVR) both in the general population and in patients with type 2 diabetes mellitus (DM-2). Until now no effective treatment is known to decrease the levels of Lp (a) levels and thus achieve a reduction of CVR. Among the new antidiabetic drugs are GLP-1Receptor agonists(GLP-1R). In addition to lowering blood glucose, these drugs have other beneficial effects. In our laboratory we have demonstrated that both native GLP-1 and various GLP-1R agonsits reduce the synthesis of Lp (a) in hepatocytes. The objective of the study is to test in humans the results observed in vitro. We will analyze whether treatment with GLP-1R agonists (Liraglutide, Exenatide or Lixisenatida) will reduce serum levels of Lp (a) in patients with DM-2.

Background: Lipoprotein (a) \[Lp (a)\] is an independent cardiovascular risk (CVR) both in the general population and in patients with type 2 diabetes mellitus (DM-2). Until now no effective treatment is known to decrease the levels of Lp (a) levels and thus achieve a reduction of CVR. Among the new antidiabetic drugs are GLP-1Receptor agonists(GLP-1R). In addition to lowering blood glucose, these drugs have other beneficial effects. In our laboratory we have demonstrated that both native GLP-1 and various GLP-1R agonsits reduce the synthesis of Lp (a) in hepatocytes.

Hypothesis: Treatment with GLP-1R agonists will lower the levels of Lp (a) in patients with DM-2.

Objective: The objective of the study is to confirm in humans the results observed in vitro. We will analyze whether treatment with GLP-1R agonists (Liraglutide, Exenatide or Lixisenatida) will reduce serum levels of Lp (a) in patients with DM-2.

Methods: we will evaluate 40 patients with DM-2 treated at the Endocrinology Department of the Vall d'Hebron University Hospital. The patients will be distributed in two groups according to the treatment prescribed by the endocrinologist during the visit of routine monitoring: group A (20 patients who were prescribred treatment with GLP-1R agonists) and group B (20 patients who were not prescribed this treatment). According to the current guidelines for treating DM-2, the GLP-1R agonists are situated as a second line treatment after metformin, and the treatment should be individualized according to the characteristics of each patient. (Inzucchi et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetes Care 2012; 35 (6):.. 1364-1379). Following these recommendations, the GLP-1R agonists are usually selected when there is obesity and / or very important to avoid hypoglycaemia. The decision to prescribe a GLP-1R agonist is made by the endocrinologist before and independently of the patient´s participation in the study.

Blood levels of Lp(a) will be evaluated at baseline and at 2 months (+/- 15 days). Diabetic patients who are treated with insulin, enzyme inhibitors DPP-4 (IDDP-4) or already treated with receptor agonists GLP-1, presenting with kidney and liver failure, HbA1c\> 10%, LDL-cholesterol\> 180 mg / dl and / or triglycerides\> 350 mg / dl will excluded.

Relevance: The results will identify a potential treatment for lowering levels of Lp (a) in patients with DM-2 and thus reducing cardiovascular risk associated with this lipoprotein.

Eligibility Criteria:
Inclusion Criteria:

* Type 2 diabetes
* age between 50-65 years
* written informed consent

Exclusion Criteria:

* active GLP-1R agonist, insulin or DPP-IV treatment.
* Liver failure (3lsn AST and/or ALT)
* Kidney failure (FG \<30ml/min/1,73m2),
* HbA1c\> 10%
* LDL-cholesterol\> 180 mg/dl
* Triglycerides\> 350 mg/dl