Impact of Metformin on Peripheral Arterial Calcification in Type 1 Diabetes

• Status: Recruiting
• Trial end date: 2025-02-02
• Target enrollment: 0
• Participant gender: All

Summary

Vascular calcification (VC) is a complication frequently observed in elderly, in chronic kidney disease (CKD) and in diabetes (particularly in type 1 diabetes). VC is a dynamic pathophysiological process that causes cardiovascular morbidity and is an independent risk factor of major amputation. In vitro and human observational studies have suggested a role of metformin in preventing VC. The investigators propose to test the effect of metformin treatment during two years on lower limb arterial calcification evaluated by CT-scan in patients with type 1 diabetes and without CKD.

This research is a phase III double blind randomized controlled trial consisting of 2 years double-blind treatment phase (patients randomized to metformin or placebo) in type 1 diabetic patients.

The participants and the investigators will be blinded to the study medications taken during the double-blind treatment period

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Metformin

Criteria

Inclusion Criteria:

1. Type 1 diabetes

2. Women and Men ≥ 18 years old and ≤ 80 years old with:

• Complications: diabetic retinopathy and/or nephropathy (with creatinine clearance ≥ 60 mL/mn) and/or neuropathy and/or peripheral arterial occlusive disease and/or cardiopathy and/or stroke and/or

• cardiovascular risk factors : hypertension and/or dyslipidemia (HDL < 0.35g/L or LDL > 1.9g/L or treated dyslipidemia) and/or tobacco use (old or active smoking greater than 5 pack years) and/or

• Diabetes duration >20 years

3. For women in childbearing age, effective contraception during the whole trial

4. Signed written informed consent

5. Affiliation of a social security regime (AME excluded)

Exclusion Criteria:

1. Creatinine clearance of less than 3 months <60 mL/mn (MDRD) at the inclusion time

2. Known metformin contra-indication: severe liver insufficiency -CHILD B or C, heart failure (FEVG<45%) or history of pulmonary edema, respiratory insufficiency with history of acute respiratory failure or patients receiving oxygen therapy, chronic ethylism, lactic acidosis

3. Know sensitivity to metformin or to any of its excipients or placebo excipients (lactose)

4. Indication or history of lower limb angioplasty (with stenting) and/or bypass

5. Previous treatment with metformin (within 3 months prior to inclusion)

6. HbA1c of less than 3 months >11%

7. Chronic inflammatory disease or chronic immune-suppressive drugs intake

8. Participation in an another interventional trial (Jardé 1 and 2) or in the exclusion period of any other interventional study

9. Pregnancy woman (confirmed by a sanguine beta-human chorionic gonadotropin test) or breastfeeding woman

10. Patient under legal protection measure (tutorship or curatorship) or deprived of freedom

11. Unable to consent