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

J.G. Timmons, N. Greenlaw, J.G. Boyle, N. Chaturvedi, I. Ford, M.C.G.J. Brouwers, T. Tillin, I. Hramiak, A.D. Hughes, A.J. Jenkins, B.E.K. Klein, R. Klein, T.C. Ooi, P. Rossing, C.D.A. Stehouwer, N. Sattar, H.M. Colhoun, J.R. Petrie*, REMOVAL Study Grp

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Web of Science)

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.
Original languageEnglish
Pages (from-to)1371-1378
Number of pages8
JournalDiabetes Obesity & Metabolism
Volume23
Issue number6
DOIs
Publication statusPublished - 1 Jun 2021

Keywords

  • cardiovascular disease
  • diabetes complications
  • metformin
  • type 1 diabetes

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