Efficacy of dapagliflozin on postprandial plasma glucose in adults with type 2 diabetes: a systematic review and meta-analysis of data from randomized placebo-controlled trials

[Speaker] Daiki Watanabe:1
[Co-author] Masanori Ootaki:1, Yuki Ohta:1, Yuko Takeba:1, Noriko Makita:2, Taroh Iiri:1,2, Naoki Matsumoto:1
1:Department of Pharmacology, St. Marianna University School of Medicine, Japan, 2:Department of Endocrinology and Nephrology, Graduate School of Medicine, The University of Tokyo, Japan

Aims/Introduction: Postprandial hyperglycemia is associated with cardiovascular risk and increase of mortality in both patients with type 2 diabetes mellitus (T2DM) and impaired glucose tolerance. To estimate the effects of dapagliflozin on 2h-postprandial plasma glucose (PPG), we conducted systematic review and performed a meta-analysis using database from randomized controlled trial (RCT) in T2DM patients.
Materials and Methods: This study of systematic review and meta-analysis is conducted in compliance with the guideline PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis). The protocol of this study was registered with the PROSPERO database and assigned an identifier CRD42016046911. A comprehensive literature search was conducted in Medline, CENTRAL and to October 5th, 2016 without language restrictions. Inclusion criteria were defined as RCTs (Randomized Control Trials), approved dapagliflozin dosing (5 mg or 10 mg), trial length ≥12 weeks, patients with T2DM (age ≥18), and reporting the 2h-PPG change from baseline to endpoint. Two reviewers working independently extracted relevant data and carried out study quality assessments using the Cochrane Risk of Bias Tool. Statistical analysis was calculated weighted mean differences (WMDs) and odds ratio (ORs) using a random-effects model. Heterogeneity was assessed with the I2 statistics.
Results: The analyses included data from 12 published trials (3,270 participants). Most of the included studies were high in quality, with low risk of bias. There were some studies where risk of bias could not be judged due to inadequate information. All the studies were funded by pharmaceutical companies. Compared with the placebo, dapagliflozin combined with or without other antidiabetic drugs improved 2h-PPG (WMDs -2.46 mmol/L; 95% CI -2.82 to -2.11; I2 =64%). However, dapagliflozin increased the risk of genital tract infection compared with placebo (OR 2.80; 95% CI 1.56 to 5.01; I2 =0%).
Conclusions: Dapagliflozin improves 2h-PPG in patients with T2DM, although it increases the risk of genital tract infection.
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