Dapagliflozin add-on therapy to metformin did not significantly improve flow-mediated dilation compared to increasing the metformin dose in the overall population of patients with early-stage type 2 diabetes (p=0.09).
RCT (n=80)
Open-label, blinded-endpoint
computer-based dynamic allocation
Yes
Does dapagliflozin added to metformin improve flow-mediated dilation compared to increasing the metformin dose in patients with early-stage type 2 diabetes mellitus?
Dapagliflozin added to metformin did not significantly improve endothelial function overall compared to high-dose metformin, but it showed benefit in patients with inadequately controlled early-stage T2DM (HbA1c ≥7.0%) and significantly reduced oxidative stress.
Absolute Event Rate: 0.85% vs -0.19%
p-value: p=0.09
BACKGROUND: Recent studies reported that sodium glucose cotransporter 2 (SGLT2) inhibitors can potentially reduce the risk of cardiovascular mortality in patients with type 2 diabetes mellitus (T2DM). However, there is little or no information on the therapeutic effects of SGLT2 inhibitors on the progression of atherosclerosis. This dapagliflozin effectiveness on vascular endothelial function and glycemic control (DEFENCE) study was designed to determine the effects of dapagliflozin, a SGLT2 inhibitor, on endothelial function in patients with early-stage T2DM. METHODS: DEFENCE is a prospective, randomized, open-label, blinded-endpoint, parallel-group, comparative clinical trial. Between October 2015 and August 2016, 80 T2DM patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0 and 7.0% showed significant improvement of FMD in the dapagliflozin group than metformin group (P < 0.05). HbA1c, fasting plasma glucose, plasma glucagon, and body weight significantly decreased in both groups. Interestingly, urine 8-hydroxy-2'-deoxyguanosin, a biomarker of oxidative stress, was significantly lower in the dapagliflozin group than metformin group at 16 weeks (P < 0.001). CONCLUSIONS: Dapagliflozin add-on therapy to metformin for 16 weeks improved endothelial function, as assessed by FMD, in patients with inadequately controlled early-stage T2DM. Improvement in oxidative stress may contribute to the improvement in FMD. Trial registration University Hospital Medical Information Network Clinical Trial Registry (UMIN000018754).
Shigiyama et al. (Thu,) conducted a rct in early-stage type 2 diabetes mellitus (n=80). Dapagliflozin vs. Metformin 1500 mg/day was evaluated on Change in flow-mediated dilation (FMD) from baseline to week 16 (p=0.09). Dapagliflozin add-on therapy to metformin did not significantly improve flow-mediated dilation compared to increasing the metformin dose in the overall population of patients with early-stage type 2 diabetes (p=0.09).