Exenatide Once Weekly, Cardiovascular Risk and Type-2 Diabetes

NCT02380521 | Completed Phase 4

• 1 other identifier: ESR-14-10139
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The glucagon-like peptide 1 (GLP-1) agonist exenatide represents an effective therapy in patients with type 2 diabetes mellitus (T2DM), which also seems to have some important non-glycemic effects. Yet, these non-glycemic effects are still largely unknown. The effect of exenatide once weekly was investigated in controlled, blinded and open-label clinical studies in subjects with T2DM who were controlled on diet and exercise alone or in combination with oral antidiabetic agents, but also in multi-dose controlled studies and such studies resulted in significant reductions in glycemic parameters (mean glycated hemoglobin (HbA1c), fasting serum/plasma glucose as well as postprandial plasma glucose levels), but also in body weight, over 24 to 30 weeks. Meaningful reductions were observed as early as week 4 of treatment, and maintained through 6 years of treatment. The study investigating cardiovascular effects of exenatide once weekly is currently undergoing. The results available are not numerous (such as DURATION-2, DURATION-3, DURATION-4 studies) and cannot lead to definitive conclusions. In this study the investigators will evaluate the effect of exenatide once-weekly on multiple cardiovascular risk markers. These markers are related to subclinical atherosclerosis, endothelial dysfunction, oxidative stress and atherogenic lipoproteins. The investigators will perform an open label, single-arm, prospective, intervention study using exenatide once weekly for a period of 8 months on 60 patients with T2DM.

Conditions

Type 2 Diabetes Mellitus

Keywords

Exenatide once weekly; T2DM; IMT; Atherogenic lipoproteins

Outcome Measures

Primary Outcomes (1)

• Subclinical atherosclerosis (as measured by cIMT) in patients with T2DM treated with exenatide once weekly

  Reduction in cIMT after 8 months of the treatment

  Change from baseline to 8 months of the treatment

Secondary Outcomes (3)

• Atherogenic lipoproteins (as measured by the analysis of 11 distinct lipoprotein subclasses using the Lipoprint system®) in patients with T2DM treated with exenatide once weekly

  Change from baseline to 8 months of the treatment

• Oxidative stress (as measured by markers of oxidative stress) in patients with T2DM treated with exenatide once weekly

  Change from baseline to 8 months of the treatment

• Endothelial dysfunction (as measured by flow mediated dilation of brachial artery) in patients with T2DM treated with exenatide once weekly

  Change from baseline to 8 months of the treatment

Study Arms (1)

60 patients with T2DM

EXPERIMENTAL

These patients will be treated with exenatide once weekly for a period of 8 months

Drug: Exenatide once weekly (BYDUREON™)

Interventions

Exenatide once weekly (BYDUREON™) DRUG

Exenatide is considered investigational medicinal product (IMP) and will be prescribed to enrolled patients in accordance with local requirements. Exenatide will be available at a fixed dose of 2 mg and supplied as a kit. Exenatide should be injected subcutaneously (SC) in the thigh, upper arm (deltoid region) or abdomen. The injection site does not have to be consistent throughout the study. Injection can be done at any time of the day irrespective of meals. It is recommended that the time of injection is consistent throughout the study. Subjects will be instructed to perform an air shot before the first injection. Subjects will follow a fixed dose of 2 mg

Also known as: BYDUREON™

60 patients with T2DM

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures;
• Men and women with T2DM aged \>18 years;
• BMI \>25 kg/m2;
• HbA1c 7.5-8.5 %;
• Receiving metformin therapy (doses ranging from 1500 to 3000 mg daily) for at least 8 weeks.

You may not qualify if:

• Pregnancy or willingness to become pregnant;
• Moderate and severe liver dysfunction;
• Moderate and severe renal failure;
• Previous major cardiovascular event;
• Severe infections at the discretion of the investigator (such as human immunodeficiency virus \[HIV\], hepatitis B virus \[HBV\] and hepatitis C virus \[HCV\]);
• Any malignancy;
• Plasma triglycerides \>400 mg/dL, plasma LDL-cholesterol \> 250 mg/dL.

Sponsors & Collaborators

• University of Palermo: lead
• AstraZeneca: collaborator

Study Sites (1)

University Hospital of Palermo

Palermo, 90127, Italy

Location

Related Publications (6)

• Drucker DJ, Buse JB, Taylor K, Kendall DM, Trautmann M, Zhuang D, Porter L; DURATION-1 Study Group. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008 Oct 4;372(9645):1240-50. doi: 10.1016/S0140-6736(08)61206-4. Epub 2008 Sep 7.

  PMID: 18782641 BACKGROUND

• Bergenstal RM, Wysham C, Macconell L, Malloy J, Walsh B, Yan P, Wilhelm K, Malone J, Porter LE; DURATION-2 Study Group. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010 Aug 7;376(9739):431-9. doi: 10.1016/S0140-6736(10)60590-9. Epub 2010 Jun 26.

  PMID: 20580422 BACKGROUND

• Diamant M, Van Gaal L, Stranks S, Northrup J, Cao D, Taylor K, Trautmann M. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet. 2010 Jun 26;375(9733):2234-43. doi: 10.1016/S0140-6736(10)60406-0.

  PMID: 20609969 BACKGROUND

• Russell-Jones D, Cuddihy RM, Hanefeld M, Kumar A, Gonzalez JG, Chan M, Wolka AM, Boardman MK; DURATION-4 Study Group. Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): a 26-week double-blind study. Diabetes Care. 2012 Feb;35(2):252-8. doi: 10.2337/dc11-1107. Epub 2011 Dec 30.

  PMID: 22210563 BACKGROUND

• Blevins T, Pullman J, Malloy J, Yan P, Taylor K, Schulteis C, Trautmann M, Porter L. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011 May;96(5):1301-10. doi: 10.1210/jc.2010-2081. Epub 2011 Feb 9.

  PMID: 21307137 BACKGROUND

• Buse JB, Nauck M, Forst T, Sheu WH, Shenouda SK, Heilmann CR, Hoogwerf BJ, Gao A, Boardman MK, Fineman M, Porter L, Schernthaner G. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet. 2013 Jan 12;381(9861):117-24. doi: 10.1016/S0140-6736(12)61267-7. Epub 2012 Nov 7.

  PMID: 23141817 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Officials

• Giuseppe Montalto, MD

  University of Palermo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 15, 2015
• First Posted: March 5, 2015
• Study Start: January 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: November 1, 2016
• Last Updated: November 8, 2016

Record last verified: 2016-11

Locations

IT (1)