Dapagliflozin increases retinal thickness in type 2 diabetic patients as compared with glibenclamide: A randomized controlled trial.

AIM: In patients with type 2 diabetes mellitus (T2DM) a progressive thinning in the central retinal thickness (CRT) is mainly related to neuroretinal degeneration and occurs before the decline in visual acuity or capillary density. We investigated the change in CRT by optical coherence tomography (OCT) in T2DM patients after 12 weeks of treatment with dapagliflozin or glibenclamide. METHODS: Ninety-seven patients (57 ± 7 years) with T2DM and clinical or subclinical atherosclerosis were randomized 1:1 to dapagliflozin (10 mg/day) or glibenclamide (5 mg/day) on top of metformin XR 1.5 g/day. OCT was obtained in all patients enrolled in the study, both at the time of randomization and at the end of the study. RESULTS: Baseline and post-treatment values of fasting glucose and glycated hemoglobin were equivalent in the two arms. There was no difference in change in diabetic retinopathy status after therapy. The center subfield thickness changed by +2(6)µm in the dapagliflozin group and by -1(7) µm in the glibenclamide group (P = 0.001). CONCLUSION: A short-term treatment with dapagliflozin may increase CRT as compared with equivalent glycemic control with glibenclamide.

Assessment of dapagliflozin effect on diabetic endothelial dysfunction of brachial artery (ADDENDA-BHS2 trial): rationale, design, and baseline characteristics of a randomized controlled trial.

BACKGROUND: Endothelial dysfunction (ED) is a hallmark in type 2 diabetes mellitus (T2DM) that favor both atherogenesis and ischemia and reperfusion injury (IRI). Sodium-glucose-2 co-transporter inhibitors (SGLT2i) may hypothetically improve microvascular and macrovascular functions via a broad spectrum of mechanisms, being superior to traditional antidiabetic therapy such as sulfonylurea, even in subjects under equivalent glycemic control. Hence, the present clinical trial was designed to compare the effect of these two treatments on markers of arterial wall function and inflammation in T2DM patients as well as on the potential mediating parameters. METHOD AND RESULTS: ADDENDA-BHS2 is a prospective, single-center, active-controlled, open, randomized trial. Ninety-eight participants (40-70 years old) with HbA1c 7-9% were randomized (1:1, stratified by gender, BMI and HbA1c levels) to either dapagliflozin 10 mg/day or glibenclamide 5 mg/day on top of metformin. The primary endpoint was the change of flow-mediated dilation (FMD) after a 12-week period of treatment evaluated at rest and after IRI between dapagliflozin and glibenclamide arms. Secondary outcomes were defined as the difference between treatments regarding: plasma nitric oxide (NO) change after FMD, plasma isoprostane, plasma levels of vascular inflammatory markers and systemic inflammatory markers, plasma levels of adipokines, anthropometric measures, glucose control parameters, office and ambulatory BP control. Safety endpoints were defined as systolic and diastolic function assessed by echocardiography and retinopathy change. Serious adverse events were recorded. The study protocol was approved by the Independent Scientific Advisory Committee. CONCLUSION: The ADDENDA-BHS2 trial is an investigator-initiated clinical trial comparing the effect of dapagliflozin versus glibenclamide on several aspects of vascular function in high cardiovascular risk T2DM patients. Besides, a large clinical and biochemical phenotype assessment will be obtained for exploring potential mediations and associations.Trial registration Clinical trial registration: NCT02919345 (September, 2016).