Metformin in adults with type 1 diabetes: design and methods of REducing with MetfOrmin Vascular Adverse Lesions (REMOVAL): an international multicentre trial

Petrie, J.R. et al. (2017) Metformin in adults with type 1 diabetes: design and methods of REducing with MetfOrmin Vascular Adverse Lesions (REMOVAL): an international multicentre trial. Diabetes, Obesity and Metabolism, 19(4), pp. 509-516. (doi: 10.1111/dom.12840) (PMID:27935183) (PMCID:PMC5357575)

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Introduction: Cardiovascular (CV) disease is a major cause of reduced life expectancy in type 1 diabetes (T1D). Intensive insulin therapy prevents CV complications but is constrained by hypoglycaemia and weight gain. Adjunct metformin reduces insulin dose requirement and stabilises weight but there are no data on its cardiovascular effects. Aims: We have initiated an international double-blind, randomized, placebo-controlled trial (REMOVAL: REducing with MetfOrmin Vascular Adverse Lesions in type 1 diabetes) to examine whether metformin reduces progression of atherosclerosis in adults with T1D. Individuals ≥40 years of age with T1D for ≥5 years are eligible if they have ≥3 of 10 specified CV risk factors. The enrolment target is 500 participants in 17 international centres. Materials and Methods: After 12 weeks single-blind placebo-controlled run-in, participants with ≥70 % adherence are randomized to metformin or matching placebo for three years with insulin titrated towards HbA1c 7.0% (53 mmol/mol)]. The primary endpoint is progression of averaged mean far wall common carotid intima-media thickness (cIMT) measured by ultrasonography at baseline, 12, 24 and 36 months. This design provides 90% power to detect a mean difference of 0.0167 mm in cIMT progression between treatment arms (α = 0.05), assuming up to 20% withdraw or discontinue treatment. Other endpoints include HbA1c, weight, LDL cholesterol, insulin requirement, progression of retinopathy, endothelial function and frequency of hypoglycaemia. Results and Conclusions: REMOVAL is the largest clinical trial of adjunct metformin therapy in T1D to date and will provide clinically meaningful information on its potential to impact CV disease and other complications.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Ford, Professor Ian and Petrie, Professor John and Sattar, Professor Naveed
Authors: Petrie, J.R., Chaturvedi, N., Ford, I., Hramiak, I., Hughes, A.D., Jenkins, A.J., Klein, B., Klein, R., Ooi, T.C., Rossing, P., Sattar, N., Stehouwer, C.D.A., and Colhoun, H.M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:Diabetes, Obesity and Metabolism
ISSN (Online):1463-1326
Published Online:09 December 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Diabetes, Obesity and Metabolism 19(4):509-516
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
560151REMOVAL study: REducing with Metformin microvascular Outcomes and VAscular complications in T1DMJohn PetrieJuvenile Diabetes Foundation (JUVDIAFO)17-2011-272RI CARDIOVASCULAR & MEDICAL SCIENCES