Can a Diabetes Drug Improve Atherosclerosis Risk?

Metformin does not improve atherosclerosis risk in patients with type 1 diabetes, according to the results of a recent study.

Although metformin may reduce insulin requirement and improve glycaemia in patients with type 1 diabetes, little data exists on potential cardiovascular (CV) benefits for patients with increased CV risk.
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From December 14, 2011, to June 24, 2014, the double-blind, placebo-controlled REMOVAL trial was conducted at 23 hospital diabetes clinics in Australia, Canada, Denmark, the Netherlands, and the United Kingdom. The researchers evaluated 493 adult participants aged 40 years or older who had type 1 diabetes for at least 5 years and demonstrated at least 3 of 10 specific CV risk factors.

Participants were randomly assigned to either twice-daily 1000 mg oral metformin (n = 219) or placebo (n = 209).

The primary outcome, measured via repeated measures regression, was progression of common carotid artery intima-media thickness (cIMT), a characteristic symptom experienced by patients with atherosclerosis.

Secondary outcomes included Hemoglobin A_1c (HbA_1c), low-density lipoprotein cholesterol (LDL-C), estimated glomerular filtration rate (eGFR), incident microalbuminuria (which was not reported), incident retinopathy, bodyweight, insulin dose, and endothelial function.

Results indicated that progression of cIMT was not significantly reduced with metformin use. However, metformin had significantly reduced maximal cIMT and HbA_1c over an average of 3 years.

After 3 years, body weight and LDL-C were reduced with metformin, and eGFR was increased. Insulin requirement was not reduced, but the researchers found a significant visit-by-treatment interaction. Additionally, the researchers observed no effect on endothelial function or retinopathy, and there was no increase in hypoglycemia.

 “These data do not support use of metformin to improve [glycemic] control in adults with long-standing type 1 diabetes as suggested by current guidelines, but suggest that it might have a wider role in cardiovascular risk management,” the researchers concluded.

—Christina Vogt

Reference:

Petrie JR, Chaturvedi N, Ford I, et al; REMOVAL Study Group. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial [Published online June 11, 2017]. Diabetes Endocrinol. doi:10.1016/S2213-8587(17)30194-8.