Dapagliflozin significantly improved resting 1-minute flow-mediated dilation by 3.3% compared to a 1.2% decrease with glibenclamide in patients with type 2 diabetes and subclinical carotid atherosclerosis.
RCT (n=98)
Open-label
1:1
No
Does dapagliflozin improve endothelial function in patients with type 2 diabetes and subclinical carotid atherosclerotic disease compared to glibenclamide?
Dapagliflozin significantly improved macro- and microvascular endothelial function compared to glibenclamide in patients with type 2 diabetes and subclinical atherosclerosis, independent of glycemic control.
Absolute Event Rate: 3.3% vs -1.2%
p-value: p=0.0001
BACKGROUND: The glucose-lowering independent effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on arterial wall function has not yet been clarified. This study aims to assess whether SGLT2i treatment can attenuate endothelial dysfunction related to type 2 diabetes mellitus (T2D) compared with glucose-lowering equivalent therapy. METHODS: In a prospective, open-label, single-center, randomized clinical trial, 98 patients with T2DM and carotid intima-media thickness above the 75th percentile were randomized 1:1 to 12 weeks of therapy with dapagliflozin or glibenclamide in addition to metformin in glucose-lowering equivalent regimens. The coprimary endpoints were 1-min flow-mediated dilation (FMD) at rest and 1-min FMD after 15 min of ischemia followed by 15 min of reperfusion time (I/R). RESULTS: Ninety-seven patients (61% males, 57 ± 7 years) completed the study. The median HbA1c decreased by - 0.8 (0.7)% and -0.7 (0.95)% following dapagliflozin and glibenclamide, respectively. The first coprimary endpoint, i.e., rest FMD changed by + 3.3(8.2)% and - 1.2(7.5)% for the dapagliflozin and glibenclamide arms, respectively (p = 0.0001). Differences between study arms in the second coprimary endpoint were not significant. Plasma nitrite 1 min after rest FMD was higher for dapagliflozin 308(220) nmol/L than for glibenclamide (258110 nmol/L; p = 0.028). The resistive indices at 1 min 0.90 (0.11) vs. 0.93 (0.07); p = 0.03 and 5 min 0.93 (0.07) vs. 0.95 (0.05); p = 0.02 were higher for the glibenclamide group than for the dapagliflozin group. Plasma biomarkers for inflammation and oxidative stress did not differ between the treatments. CONCLUSIONS: Dapagliflozin improved micro- and macrovascular endothelial function compared to glibenclamide, regardless of glycemic control in patients with T2DM and subclinical carotid atherosclerotic disease.
Spósito et al. (Fri,) conducted a rct in Type 2 diabetes mellitus with subclinical carotid atherosclerotic disease (n=98). Dapagliflozin vs. Glibenclamide (5 mg/day) was evaluated on Change in 1-min flow-mediated dilation (FMD) at rest (p=0.0001). Dapagliflozin significantly improved resting 1-minute flow-mediated dilation by 3.3% compared to a 1.2% decrease with glibenclamide in patients with type 2 diabetes and subclinical carotid atherosclerosis.