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DAPAGLIFLOZIN EFFECT ON ENDOTHELIAL DYSFUNCTION IN DIABETIC PATIENTS WITH ATHEROSCLEROTIC DISEASE: A RANDOMIZED ACTIVE-CONTROLLED TRIAL
Meta-analysis based on clinical trials suggested that sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk of myocardial infarction in individuals with prior manifestation of coronary events but not in those with uneventful clinical history. Impaired endothelial function is one of the first disorders detected in atherogenesis and can be modified early by prevention therapies. In this case, flow-mediated dilation (FMD) of the brachial artery is a preferred method for assessing endothelial function owing to its noninvasiveness, close correlation to coronary endothelial function and association with the incidence of long-term coronary events. So, 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.
Material e Método
The ADDENDA-BHS2 was a randomized, open-label, single-center study. Eligible patients were 40–70 years of age. Inclusion criteria included a glycated hemoglobin (HbA1c) level between 7 and 9%, the use of ≤ two oral hypoglycemic agents and the presence of atherosclerotic disease. Patients who remained eligible were randomly assigned to a 12-week treatment phase at a 1:1 ratio to dapagliflozin (10 mg/day) or glibenclamide (5 mg/day) on top of their ongoing metformin use. The coprimary endpoints were 1-min FMD at rest and 1-min FMD after 15 min of ischemia followed by 15 min of reperfusion time (I/R).
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 (258 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.
Discussão e Conclusões
The ADDENDA-BHS2 trial demonstrated that dapagliflozin treatment improves macro- and microvascular endothelial function in diabetic individuals presenting with atherosclerotic disease.
Sodium-glucose cotransporter-2 inhibitors, Endothelial dysfunction, flow-mediated dilation, type 2 diabetes
UNICAMP - São Paulo - Brasil
ISABELLA BONILHA, Ikaro Breder, Alexandre Soares, Sheila Kimura-Medorima, Daniel Munhoz, Riobaldo Cintra, Luiz Sergio Carvalho, Thiago Quinaglia, Andrei Carvalho Sposito