Metformin and carotid intima-media thickness in never-smokers with type 1 diabetes: the REMOVAL trial

Timmons, J. G. et al. (2021) Metformin and carotid intima-media thickness in never-smokers with type 1 diabetes: the REMOVAL trial. Diabetes, Obesity and Metabolism, 23(6), pp. 1371-1378. (doi: 10.1111/dom.14350) (PMID:33591613)

Abstract

Aim: To determine whether metformin's effects on carotid artery intima‐media thickness (cIMT) in type 1 diabetes differ according to smoking status. Methods: Regression model effect estimates for the effect of metformin versus placebo (double‐blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial. Results: In 428 randomized participants (227 never‐smokers, 201 ever‐smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never‐smokers (−0.012 mm, 95% CI −0.021 to −0.002; p = .0137) but not in ever‐smokers (0.003 mm, 95% CI −0.008 to 0.014; p = .5767); and similarly in non‐current smokers (−0.008 mm, 95% CI −0.015 to −0.00001; p = .0497) but not in current smokers (0.013 mm, 95% CI −0.007 to 0.032; p = .1887). Three‐way interaction terms (treatment*time*smoking status) were significant for never versus ever smoking (p = .0373, prespecified) and non‐current versus current smoking (p = .0496, exploratory). Averaged maximal carotid IMT progression (per year) was reduced by metformin versus placebo in never‐smokers (−0.020 mm, 95% CI −0.034 to −0.006; p = .0067) but not in ever‐smokers (−0.006 mm, 95% CI −0.020 to 0.008; p = .4067), although this analysis was not supported by a significant three‐way interaction term. Conclusions: This subgroup analysis of the REMOVAL trial provides additional support for a potentially wider role of adjunct metformin therapy in cardiovascular risk management in type 1 diabetes, particularly for individuals who have never smoked cigarettes.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Boyle, Dr James and Petrie, Professor John and Timmons, Dr Joseph and Greenlaw, Miss Nicola and Sattar, Professor Naveed and Ford, Professor Ian
• Authors: Timmons, J. G., Greenlaw, N., Boyle, J. G., Chaturvedi, N., Ford, I., Brouwers, M. C.G.J., Tillin, T., Hramiak, I., Hughes, A. D., Jenkins, A. J., Klein, B. E.K., Klein, R., Ooi, T. C., Rossing, P., Stehouwer, C. D.A., Sattar, N., Colhoun, H. M., and Petrie, J. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Diabetes, Obesity and Metabolism
• Publisher: Wiley
• ISSN: 1462-8902
• ISSN (Online): 1463-1326
• Published Online: 16 February 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Diabetes, Obesity and Metabolism 23(6): 1371-1378
• Publisher Policy: Reproduced under a Creative Commons License