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

Diabetes Obes Metab. 2021 Jun;23(6):1371-1378. doi: 10.1111/dom.14350. Epub 2021 Mar 8.

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.

Keywords: cardiovascular disease; diabetes complications; metformin; type 1 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carotid Arteries
  • Carotid Intima-Media Thickness
  • Diabetes Mellitus, Type 1* / complications
  • Diabetes Mellitus, Type 1* / drug therapy
  • Double-Blind Method
  • Humans
  • Metformin* / therapeutic use
  • Risk Factors
  • Smokers
  • Smoking

Substances

  • Metformin