A Long-term Trial to Compare the Effects of Liraglutide and Sulphonylurea (Glimepiride) Both in Combination With Metformin on Clinical, Endothelial and Image Markers of Cardiovascular Risk in Patients With Type 2 Diabetes
Information source: Fundación Fernández-Cruz
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Type 2 Diabetes
Intervention: Liraglutide + metformin (Drug); Glimepiride + metformin (Drug)
Phase: Phase 4
Status: Withdrawn
Sponsored by: Fundación Fernández-Cruz Official(s) and/or principal investigator(s): Alfonso Calle, MD, Principal Investigator, Affiliation: Hospital ClÃnico San Carlos, Department of Endocrinology, Metabolism and Nutrition, Spain
Summary
The process of atherosclerosis is multifactorial and involves many mechanisms. The majority
of published works have identified endothelial dysfunction as the first step in a cascade of
events that culminates in plaque formation. Among the various mechanisms that occur
following the attack on the vessel wall, it is thought that stem cells in the form of
endothelial progenitor cells (EPCs) are the endothelial protection mechanism.
Factors identified as cardiovascular risk factors, or rather those conditions which suppose
a threat to the vessel wall, should therefore be associated with low levels of EPCs. To date
this link has been shown in hypertension, diabetes, hyperlipidaemia, and smoking.
Furthermore, the lack of wall protection in situations of low levels of EPCs is clearly a
biomarker of cardiovascular morbidity and mortality.
On the other hand, the correction of a risk factor allows recuperation of EPCs and is
therefore showing itself to be a promising tool for measuring therapeutic efficacy.
The tools for correcting EPC levels are not clearly defined. The effect of statins on levels
of EPC has been shown, and the low levels of EPCs in diabetes seem to be susceptible to
treatment with statins.
The role of glucagon-like peptide (GLP-1) is slowly being elucidated but the actual
mechanism of its potential endothelial protection is unknown, and its effect on EPCs has not
been studied.
Liraglutide, a long-acting GLP-1 analogue, could also be an interesting option for long-term
vessel wall protection, but to date its ability to correct cardiovascular biomarkers such as
EPCs has not been studied.
Clinical Details
Official title: A Long-term, Randomized, Open-labeled, Parallel-group Trial to Compare the Effects of Liraglutide and Sulphonylurea (Glimepiride) Both in Combination With Metformin on Clinical, Endothelial and Image Markers of Cardiovascular Risk in Patients With Type 2 Diabetes
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label
Primary outcome: assess the effect of treatment with liraglutide compared to glimepiride, as add-on to metformin, for one year on circulating levels of EPCs in patients with type 2 diabetes poorly controlled.
Secondary outcome: assess the efficacy of liraglutide compared to glimepiride, as add-on to metformin, with regards to other surrogate biomarkers of cardiovascular risk: IMT, Central BP, CD40L, hsCRP, Lp-PLA2, BNP.Relationship between EPC levels and all these biomarkers in patients treated with liraglutide compared to those treated with glimepiride. Safety parameters of glycaemic control: HbA1c, FPG
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Informed written consent obtained before any trial-related activities (trial-related
activities are any procedures that would not have been performed during normal
management of the subject).
- Male or female patients between 18 and 75 years old;
- Subjects diagnosed with type 2 diabetes for more than 1 year
- Insulin naïve subjects (Allowed are: Previous short term insulin treatment < 28 days
in total; Treatment during hospitalisation or during gestational diabetes is allowed
for periods < 14 days in total)
- Subjects previously treated with metformin at a minimum dose of 1500 mg/day
- HbA1c from 7% to 9%
- Adherence to injection therapy
Exclusion Criteria:
- Type 1 diabetic patients;
- Use of a GLP-1 receptor agonist (exenatide, liraglutide or other), pramlintide,
thiazolidinediones or any DPP-4 inhibitor within the 3 months prior to screening;
- Females of childbearing potential who are pregnant, breast-feeding or intend to
become pregnant or are not using adequate contraceptive methods (or their partners).
Adequate contraceptive measures are considered the use of hormonal based
contraceptives in combination with a barrier contraception,
- Patients with a clinical history of serious cardiovascular events in the last 3
months (myocardial infarction, unstable angina, cerebral infarction, TIA, peripheral
arteriopathic event);
- Suspected or confirmed acute pancreatitis;
- Personal history of medullary thyroid carcinoma;
- Patients with congestive heart failure (NYHA I-IV);
- Moderate or severe renal failure (creatinine clearance < 60 ml/min);
- Patients with hepatic failure. This is AST or ALT > 3 times the upper limit of
normal, history of cirrhosis or hepatitis;
- Patients with cancer in the last 10 years;
- Patients with terminal diseases;
- Patients unlikely to comply with trial procedures;
- Known psychiatric disease which may interfere with study procedure;
- Any other pathology which may interfere with the study results at the investigator's
discretion;
- Known or suspected contraindications to or history of hypersensitivity to the trial
product or related products;
- Previous participation in this trial i. e. randomised;
- The receipt of any investigational product within 30 days.
Locations and Contacts
Hospital ClÃnico San Carlos, Madrid 28040, Spain
Additional Information
Starting date: May 2012
Last updated: July 1, 2013
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