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.
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Authors | Joseph G Timmons, Nicola Greenlaw, James G Boyle, Nish Chaturvedi, Ian Ford, Martijn C G J Brouwers, Therese Tillin, Irene Hramiak, Alun D Hughes, Alicia J Jenkins, Barbara E K Klein, Ron Klein, Teik C Ooi, Peter Rossing, Coen D A Stehouwer, Naveed Sattar, Helen M Colhoun, John R Petrie, REMOVAL Study Group |
Journal | Diabetes, obesity & metabolism
(Diabetes Obes Metab)
Vol. 23
Issue 6
Pg. 1371-1378
(06 2021)
ISSN: 1463-1326 [Electronic] England |
PMID | 33591613
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | © 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. |
Chemical References |
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Topics |
- Carotid Arteries
- Carotid Intima-Media Thickness
- Diabetes Mellitus, Type 1
(complications, drug therapy)
- Double-Blind Method
- Humans
- Metformin
(therapeutic use)
- Risk Factors
- Smokers
- Smoking
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