Metformin No Help for Atherosclerosis in T1D

SAN DIEGO — Metformin didn’t help diminish atherosclerosis in patients with type 1 diabetes, according to results of the REMOVAL trial.

Compared with placebo, 1,000 mg twice-daily of oral metformin didn’t reduce mean progression of common carotid artery intima-media thickness (cIMT) over 3 years (-0.005 mm per year, 95% CI -0.012 to 0.002; P=0.1664), John Petrie, PhD, of the University of Glasgow in Scotland, and colleagues reported here at the American Diabetes Association and simultaneously in The Lancet Diabetes & Endocrinology.

They did find, however, that one of the trial’s tertiary endpoints – maximal cIMT — was significantly reduced among the treatment group (-0.013 mm per year, -0.024 to -0.003; P=0.0093).

Vivian Fonseca, MD, of Tulane University School of Medicine, who wasn’t involved with the study, told MedPage Today that this tertiary endpoint represents a “small change, and we don’t quite know what that means in terms of long-term cardiovascular outcomes.”

Some work has shown that metformin can reduce the need for insulin and improve glycemic control in patients with type 1 diabetes, but less is known about whether it confers cardiovascular protection. To explore that issue, Petrie and colleagues conducted the REMOVAL trial across 23 centers in five countries. The randomized, double-blind study included 428 participants with type 1 diabetes for a minimum of 5 years (n=219 treatment; n=209 placebo). All participants, who had met three out of ten pre-specified CV-risk factors, had endured a 3-month optimization period regarding glycemic and risk factor control prior to randomization.

Regarding the first secondary outcome, HbA1c improved over 3 years among the metformin group versus the placebo (-0.13%, 95% CI -0.22 to -0.037; P=0.006). However, this change was attributed to a reduction after 3 months (-0.24%, -0.34 to -0.13; P<0.0001) and was not sustained long-term, they reported (P=0.0163 for visit-by-treatment interaction).

Three years of metformin…

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