Effect of GLP-1 on Angiogenesis

NCT ID: NCT02686177

Last Updated: 2021-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-18
• Study Completion Date: 2021-05-28

Brief Summary

GLP-1 receptor agonists are introduced in the treatment of type 2 Diabetes (T2D) and their efficacy is documented. However, safety aspects are also important to evaluate with respect to micro and macrovascular complications associated with T2D. Few studies have properly addressed the role of GLP-1-based therapies in regulating vascular integrity and angiogenesis. The study evaluate the impact of one-month treatment Liraglutide on both ANGPT2 and ANGLPT4 levels and endothelial circulating progenitor cells, angiogenesis biomarkers in type 2 diabetic patients.

Detailed Description

GLP-1 receptor agonists are introduced in the treatment of type 2 Diabetes (T2D) and their efficacy is documented. Beside their therapeutic benefits, direct cardiovascular effects have also been reported. However, safety aspects are also important to evaluate with respect to micro and macrovascular complications associated with T2D. T2D patients treated with GLP-1 analogs may suffer from microvascular complications such as macular oedema and proliferative retinopathy, characterized by excessive retinal angiogenesis. Few studies have properly addressed the role of GLP-1-based therapies in regulating vascular integrity and angiogenesis. The role of GLP-1 on endothelial cell (EC) growth, EC integrity and angiogenesis thus needs to be characterized. Our aim is to provide the proof of concept that agonists of GLP-1 regulate angiogenesis in humans and identify the underlying mechanisms. The present project is the translational part of the ANR Angiosafe-T2D, regarding clinical safety aspects of GLP-1 receptor agonists (namely Liraglutide) on angiogenesis.

The study evaluate the impact of one-month treatment Liraglutide on both ANGPT2 and ANGLPT4 levels and endothelial circulating progenitor cells, angiogenesis biomarkers in type 2 diabetic patients.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1: Liraglutide

Liraglutide 1,2 mg once daily subcutaneous injection for 1 month (4 weeks)

Group Type: EXPERIMENTAL

Liraglutide

Intervention Type: DRUG

2: Add on oral antidiabetic medication

Metformin or sulfonylurea depending on monotherapy

Group Type: ACTIVE_COMPARATOR

Metformin or sulfonylurea

Intervention Type: DRUG

Interventions

Liraglutide

Intervention Type: DRUG

Metformin or sulfonylurea

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Type 2 diabetic patients (ADA criteria)
• Age > 18 years
• Obesity (BMI >= 25 kg/m2)
• HbA1c > 6.5 %
• Treatment with Metformin and/or secretagogues
• Effective contraception (women)

Exclusion Criteria

• Treatment with Exenatide, Liraglutide or other incretinergic regimen (<1 month before recruitment)
• Type 1 diabetes
• acute disease or infection
• chronic renal failure (MDRD eGFR≤50 mL/min)
• recent cardiovascular event or surgery (<3 months)
• pancreatitis history
• anti-VEGF treatment
• untreated cancer
• immunological disorders
• pregnancy and lactation
• Vulnerable people : deprivation of Liberty safeguards
• hypersensitivity to the active substance or to any of the excipients of the investigational drug
• diabetic ketoacidosis
• heart failure stage 3 or 4 (NYHA III-IV)
• Hepatic insufficiency
• inflammatory bowel disease and gastroparesis
• No affiliation to the social security

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bénédicte GABORIT, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Marseille

Locations

Nutrition department, pole ENDO - Assistance Publique Hôpitaux Marseille

Marseille, , France

Countries

France

References

Gaborit B, Julla JB, Besbes S, Proust M, Vincentelli C, Alos B, Ancel P, Alzaid F, Garcia R, Mailly P, Sabatier F, Righini M, Gascon P, Matonti F, Houssays M, Goumidi L, Vignaud L, Guillonneau X, Erginay A, Dupas B, Marie-Louise J, Autie M, Vidal-Trecan T, Riveline JP, Venteclef N, Massin P, Muller L, Dutour A, Gautier JF, Germain S. Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study. J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgz069. doi: 10.1210/clinem/dgz069.

Reference Type: DERIVED

PMID: 31589290 (View on PubMed)

Other Identifiers

2015-002930-35

Identifier Type: OTHER

Identifier Source: secondary_id

P140710

Identifier Type: -

Identifier Source: org_study_id