Produção Nacional
Revisado por pares
Dapagliflozin effect on endothelial dysfunction in diabetic patients with atherosclerotic disease: a randomized active-controlled trial
2021; BioMed Central; Volume: 20; Issue: 1 Linguagem: Inglês
10.1186/s12933-021-01264-z
ISSN1475-2840
AutoresAndrei C. Spósito, Íkaro Breder, Alexandre Anderson de Sousa Munhoz Soares, Sheila T. Kimura-Medorima, Daniel Munhoz, Riobaldo M.R. Cintra, Isabella Bonilha, Daniela Camargo de Oliveira, Jessica Cunha Breder, Pamela Cavalcante, Camila Moreira, Filipe A. Moura, José Carlos de Lima Júnior, Helison Rafael Pereira do Carmo, Joaquim Barreto, Wilson Nadruz, Luiz Sérgio Fernandes de Carvalho, Thiago Quinaglia,
Tópico(s)Cardiovascular Function and Risk Factors
ResumoAbstract 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 (258[110] 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.
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