Objective: Recent studies showed that sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce the risk of cardiovascular events and mortality in patients with type 2 diabetes (T2D). However, the mechanisms underlying this effect remain unclear. We compared the effects of dapagliflozin, a SGLT2 inhibitor, with those of gliclazide on vascular function in patients with T2D.

Research Design and Methods: This was a prospective, randomized, blinded-endpoint, comparative clinical trial. In 2016−2017, T2D patients treated with ≥750 mg of metformin (HbA1c, 7.5%−10.0%; n = 32) were enrolled and randomized to receive either gliclazide (30 mg/day) with uptitration, or dapagliflozin (10 mg/day) for 24 weeks. The primary endpoint was a change in flow-mediated dilation (FMD) from baseline to the end of the study. The secondary outcomes included changes in pulse wave velocity (PWV), microvascular reactivity, ankle-brachial index (ABI), and carotid intima-medial thickness (IMT). Biochemical parameters related to glucose homeostasis, atherogenic dyslipidemia, oxidative stress, and adverse events, were evaluated.

Results: Glycated hemoglobin and fasting glucose levels decreased significantly in both groups. The FMD, PWV, microvascular reactivity, and ABI improved significantly in the dapagliflozin group, but not in the gliclazide group. Lipoprotein(a), oxidized LDL, and thiobarbituric acid reactive substance levels decreased, whereas LDL particle sizes increased, in the dapagliflozin group exclusively. Hypoglycemia was more common in the gliclazide group.

Conclusions: Dapagliflozin therapy for 24 weeks improved vascular function, alleviated atherogenic dyslipidemia, and decreased oxidative stress in patients with T2D. Glucose independent changes in cardiometabolic risk factors may contribute to the cardiovascular benefits observed in clinical trials with SGLT2 inhibitors.


S. Lim: None. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi.

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