A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation

Abstract

BackgroundThe sodium–glucose cotransporter 2 inhibitor, dapagliflozin, has been shown to improve diabetic control and reduce blood pressure in patients with type 2 diabetes mellitus. Its effects on micro- and macrovascular structure and function have not yet been reported.MethodsThis was a prospective, single-centre, placebo-controlled, double-blind, randomised crossover phase IIIb study conducted between March 2014 and February 2015. After a 4-week run-in/washout phase, patients (N = 59) received 6 weeks of either dapagliflozin 10 mg or placebo once daily. They then underwent a 1-week washout before crossing over to the other treatment. Changes in retinal capillary flow (RCF) and arteriole remodelling were evaluated using scanning laser Doppler flowmetry, while micro- and macrovascular parameters in the systemic circulation were assessed using pulse wave analysis.ResultsSix weeks of dapagliflozin treatment resulted in improvements in diabetes control, including blood glucose and insulin resistance, and reduced office and 24-h ambulatory blood pressure values. RCF decreased from 324 AU at baseline to 308 AU after treatment with dapagliflozin (p = 0.028), while there was little difference after the placebo (318 AU; p = 0.334). Furthermore, the arteriole remodelling that was seen after the placebo phase was not evident after the dapagliflozin phase. Central systolic and diastolic blood pressure values were significantly lower after 6 weeks of dapagliflozin, by 3.0 and 2.2 mmHg, respectively (p = 0.035 and 0.020, respectively vs. baseline).ConclusionsSix weeks of dapagliflozin treatment resulted in numerous beneficial effects. In addition to achieving superior diabetes control and blood pressure, parameters associated with the early stages of vascular remodelling were also improved. Trial registration http://www.clinicaltrials.gov (NCT02383238)

Comparisons of diabetic retinopathy events associated with glucose‐lowering drugs in patients with type 2 diabetes mellitus: A network meta‐analysis

“…However, SGLT2 inhibitors were associated with the lowest risk among the GLDs in our network meta‐analysis. Recently, several studies explored the mechanism behind the beneficial effect of SGLT2 inhibitors on DR. One small trial involving 59 patients found that dapagliflozin, 10 mg/d administered for 6 weeks, significantly lowered retinal capillary flow compared to little change in the placebo group . In addition, dapagliflozin appeared to prevent changes to the structure of the retinal arterioles .…”

“…Recently, several studies explored the mechanism behind the beneficial effect of SGLT2 inhibitors on DR. One small trial involving 59 patients found that dapagliflozin, 10 mg/d administered for 6 weeks, significantly lowered retinal capillary flow compared to little change in the placebo group . In addition, dapagliflozin appeared to prevent changes to the structure of the retinal arterioles . The beneficial effects of SGLT2 inhibitors may be explained, in part, by their blockade of the renin‐angiotensin system, by improved glycaemic control and by reduced blood pressure.…”

Cardiorenal protection with SGLT2: Lessons from the cardiovascular outcome trials

“…The composites of retinopathy were not reported in the CANVAS‐Renal study or the Declare‐TIMI58 study . However, limited dapagliflozin trials have shown that trials with this SGLT2i have beneficial outcomes in retinal arteriole remodeling assessed with Doppler flowmetry …”

Physical exercise and non‐insulin glucose‐lowering therapies in the management of Type 2 diabetes mellitus: a clinical review

“…Indeed, the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 diabetes trial (EMPA-REG) found that empagliflozin use in people with Type 2 diabetes reduced cardiovascular death by 38% and reduced hospitalization for heart failure by 35% [69]. Furthermore, dapagliflozin has recently been shown to reduce central pulse pressure and retinal capillary hyperperfusion, suggesting beneficial effects with regard to vascular function [70]. Although physical exercise improves cardiovascular and respiratory systems we found no published studies directly assessing the combined effect of SGLT2 inhibitors and exercise.…”