What is the clinical evidence from this study?

Study design: RCT. Population: early-stage type 2 diabetes mellitus (n=80). Intervention: Dapagliflozin vs. Metformin 1500 mg/day. Primary outcome: Change in flow-mediated dilation (FMD) from baseline to week 16 (p=0.09).

What question did this study set out to answer?

To determine the therapeutic effects of dapagliflozin add-on therapy versus dose-increased metformin on vascular endothelial function and glycemic parameters in patients with early-stage type 2 diabetes mellitus.

July 6, 2017Cardiovascular DiabetologyOpen Access

Effectiveness of dapagliflozin on vascular endothelial function and glycemic control in patients with early-stage type 2 diabetes mellitus: DEFENCE study

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Key result

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).

Why the study?

Does dapagliflozin added to metformin improve flow-mediated dilation compared to increasing the metformin dose in patients with early-stage type 2 diabetes mellitus?

Population

80 Japanese patients with early-stage type 2 diabetes mellitus treated for more than 12 weeks with 750 mg of…

Comparison

Dapagliflozin 5 mg/day added to metformin 750… vs Metformin dose increased from 750 mg/day to 1500…

Design

RCT, Computer-based dynamic allocation method based on the with/without…

Follow-up

16 weeks

Authors

FSFumika ShigiyamaKanazawa Medical University NKNaoki KumashiroKanazawa Medical University MMMasahiko MiyagiToho University

Discussion

Member takes

Implication

Dapagliflozin may improve endothelial function in T2DM; leaves open effects on atherosclerosis progression.

Key Points

To determine the therapeutic effects of dapagliflozin add-on therapy versus dose-increased metformin on vascular endothelial function and glycemic parameters in patients with early-stage type 2 diabetes mellitus.
Prospective, randomized, open-label, blinded-endpoint clinical trial (UMIN000018754) conducted between October 2015 and August 2016.
Enrolled 80 patients with early-stage type 2 diabetes (HbA1c 6.0% to <8.0%) receiving 750 mg/day metformin, randomized to 1500 mg/day metformin (n = 40) or 750 mg/day metformin plus 5 mg/day dapagliflozin (n = 40) for 16 weeks.
Evaluated primary outcome of change in flow-mediated dilation (FMD) along with secondary measures of glycemic indices, body composition, and oxidative stress biomarkers.
Change in flow-mediated dilation was comparable between the two treatment groups overall, but patients with baseline HbA1c >7.0% achieved significantly greater FMD improvement with dapagliflozin (P < 0.05).
Both treatment groups demonstrated significant decreases in HbA1c, fasting plasma glucose, plasma glucagon, and body weight across the 16-week period.
Urinary 8-hydroxy-2'-deoxyguanosine, a key biomarker of oxidative stress, was significantly lower in the dapagliflozin group than in the metformin group at 16 weeks (P < 0.001).

Study Design

Type

RCT (n=80)

Blinding

Open-label, blinded-endpoint

Randomization

computer-based dynamic allocation

Multicenter

Yes

Structured PICO

Does dapagliflozin added to metformin improve flow-mediated dilation compared to increasing the metformin dose in patients with early-stage type 2 diabetes mellitus?

Population

80 Japanese adults aged 20-74 with early-stage type 2 diabetes mellitus inadequately controlled on metformin, followed for 16 weeks.

Intervention

Dapagliflozin 5 mg/day added to metformin 750 mg/day for 16 weeks.

Comparator

Metformin dose increased from 750 mg/day to 1500 mg/day for 16 weeks.

Outcome

Change in flow-mediated dilation (FMD) from baseline to the end of the 16-week treatment period.surrogate

Main Result

Absolute Event Rate: 0.85% vs -0.19%

p-value: p=0.09

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.

Limitations

Open-label design study, unexpected bias might occur
Relatively small number of patients
Relatively short duration of study
Subjects had moderate hyperglycemia, effects in HbA1c >8% unknown
Only 5 mg dose of dapagliflozin was used, not 10 mg

Cite This Study

Shigiyama et al. (2017) conducted an 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).

synapsesocial.com/papers/6a6bb2079c58b04430f2dc18 https://doi.org/10.1186/s12933-017-0564-0

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Effectiveness of dapagliflozin on vascular endothelial function and glycemic control in patients with early-stage type 2 diabetes mellitus: DEFENCE study

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Effectiveness of dapagliflozin on vascular endothelial function and glycemic control in patients with early-stage type 2 diabetes mellitus: DEFENCE study

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Also Consider