Phase 3
Completed N=428
REducing With MetfOrmin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL)
Diabetes Mellitus, Type 1
Source: ClinicalTrials.gov NCT01483560 ↗
Enrolled (actual)
428
Serious AEs
15.2%
Results posted
Jun 2019
Primary outcomePrimary: Change in Averaged Mean Far Wall Common Carotid Artery Intima-media Thickness (cIMT) — 0.773; 0.791; 0.782; 0.788 mm
◆ Published Evidence
Highly cited
346citations · ~38 / year
Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial.
Summary
The trial is conducted in the United Kingdom (UK), Australia, Canada, Denmark and the Netherlands. The aim is to test whether 3 years treatment with metformin added to titrated insulin therapy (towards target HbA1c 7.0%/53 mmol/mol) reduces atherosclerosis, as measured by progression of carotid intima-media thickness (cIMT), in adults with confirmed type 1 diabetes aged 40 years and over at increased risk for cardiovascular disease.
Linked Publications (2)
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Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial.
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Metformin for preventing the progression of chronic kidney disease.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Averaged Mean Far Wall Common Carotid Artery Intima-media Thickness (cIMT) |
0.773; 0.791; 0.782; 0.788; 0.792; 0.823 | — |
| SECONDARY Change in HbA1c |
8.1; 8.0; 8.1; 8.1 | — |
| SECONDARY Change in LDL Cholesterol |
2.23; 2.25; 2.07; 2.21 | — |
| SECONDARY Change in Estimated Glomerular Filtration Rate |
92.9; 91.1; 92.1; 87.2 | — |
| SECONDARY Number of Participants With Retinopathy and at Least a 2 Stage Progression in Retinopathy From Baseline to 36 Months |
191; 190; 8; 10 | — |
| SECONDARY Change in Weight |
83.9; 83.5; 82.0; 83.2 | — |
| SECONDARY Change in Insulin Dose |
0.36; 0.68; 0.62; 0.67 | — |
| SECONDARY Change in Endothelial Function |
2.28; 2.24; 2.17; 2.24 | — |
Eligibility Criteria
Inclusion Criteria
- Type 1 Diabetes for five years or more*
- Age 40 years or above
- 7.0 = 27 kg/m^2
- Current HbA1c >8.0% (64 mmol/mol)
- Known CVD/peripheral vascular disease
- Current smoker
- Estimated glomerular filtration rate (eGFR) =140/90 millimeters of mercury (mmHg) or established on antihypertensive treatment)
- Dyslipidaemia [total cholesterol >=5.0 mmol/L (200 mg/dL);OR HDL cholesterol =1.7 mmol/L (150mg/dL); or established on lipid-lowering treatment)]
- Strong family history of CVD (at least one parent, biological aunt/ uncle, or sibling with myocardial infarction or stroke aged 20 years
Exclusion Criteria
- eGFR < 45 ml/min/1.73m2
- woman of childbearing age not on effective contraception
- Pregnancy and/or lactation
- Acute coronary syndrome or Stroke/Transient Ischaemic Attack within the last three months
- NYHA stage 3 or 4 heart failure
- Significant hypoglycaemia unawareness
- Impaired cognitive function/ unable to give informed consent
- Previous carotid surgery/ inability to capture adequate carotid images
- Estimated glomerular filtration < 45ml/min/1.73m^2 (MDRD)
- Gastroparesis
- History of lactic acidosis
- Other contraindications to metformin (hepatic impairment, known hypersensitivity to metformin, acute illness such as dehydration, severe infection, shock, acute cardiac failure or suspected tissue hypoxia)
- Any coexistent life threatening condition including prior diagnosis of cancer within two years
- History of alcohol problem or drug abuse
Data sourced from ClinicalTrials.gov (NCT01483560) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.