Dapagliflozin Improves Endothelial Function in Type 2 Diabetes

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Dapagliflozin may reduce oxidative stress.
Dapagliflozin may reduce oxidative stress.

This article is part of Endocrinology Advisor's coverage of the American Diabetes Association's 77th Scientific Sessions (ADA 2017), taking place in San Diego, CA. Our staff will report on medical research and technological advances in diabetes and diabetes education, conducted by experts in the field. Check back regularly for more news from ADA 2017.


Dapagliflozin improved endothelial function in patients with type 2 diabetes, according to results of the DEFENCE clinical trial, presented at the American Diabetes Association 77th Scientific Sessions, June 9-13, in San Diego, California.

The multicenter, prospective, open-label, randomized, parallel clinical trial was conducted by researchers in Japan to investigate the therapeutic effects of sodium glucose cotransporter 2 (SGLT2) inhibitors on atherosclerosis and endothelial function.

Patients with type 2 diabetes (n=80) who had glycated hemoglobin A1c (HbA1c) levels ≥6% and <8.0% were randomly assigned to 750 mg of metformin supplemented with 5 mg of dapagliflozin (dapagliflozin group) or 1500 mg of metformin (metformin group) for 16 weeks. Researchers used flow mediated dilation to measure endothelial function.

Changes from baseline in glycemic control, lipid levels, body composition, and atherosclerosis-related markers (eg, oxidative stress) were compared between the treatment groups.

Flow mediated dilation changes were comparable between the groups, but particularly tended to improve in the dapagliflozin group. Patients with HbA1c >7% in the dapagliflozin group had significant improvements in flow mediated dilation vs the metformin group (1.05±2.59% vs –0.94±2.39%, respectively; P <.05).

Both groups had significant decreases in HbA1c, fasting plasma glucose and plasma glucagon levels, and in body weight. In addition, the dapagliflozin group had significant decreases in levels of an oxidative stress biomarker, urine 8-OHdG, compared with the metformin group (–0.63±1.82 vs 1.13±2.17 ng/mg, respectively; P <.001).

"[T]his is the first study to reveal the effect of dapagliflozin on prevention of early progression of atherosclerosis," the researchers concluded. "The reduction of oxidative stress may contribute to the improvement of [flow mediated dilation]."

Disclosures: Drs Kumashiro and Hirose report financial relationships with multiple pharmaceutical companies, including Novo Nordisk. 


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Reference

Shigiyama F, Kumashiro N, Miyagi M, et al. Clinical trial for effectiveness of dapagliflozin on vascular endothelial function and glycemic control in type 2 diabetes mellitus patients: DEFENCE study. Abstract 12-LB. Presented at: the 77th Annual American Diabetes Association 77th Scientific Sessions. June 9-13, 2017; San Diego, CA.

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