Efficacy and safety of ipragliflozin as add-on to metformin for type 2 diabetes: a meta-analysis of double-blind randomized controlled trials

ABSTRACT

Objectives: To evaluate the efficacy and safety of ipragliflozin as add-on therapy to metformin in patients with type 2 diabetes mellitus.

Methods: Systematic literature searches were performed in several databases across PubMed, the Cochrane Central Register of Controlled Trials, Embase, Medline, ClinicalTrials.gov, PsycINFO, and Web of Science from inception to 12 March 2019. After the extraction of data from eligible studies, randomized controlled trials (RCTs) were assessed for quality and analyzed statistically. Standardized mean difference (SMD) and risk ratio (RR) with 95% CIs were used to evaluate efficacy and safety end-points. Sensitivity analyses and subgroup analyses based on intervention times were also performed.

Results: Five RCTs with 847 patients were included. Compared to metformin alone, ipragliflozin as an adjuvant to metformin reduced glycated hemoglobin (HbA1c) in 12 weeks and 24 weeks, respectively [12 w: SMD −0.30, 95% CI −0.51 to −0.10%, p = 0.004; 24 w: SMD −0.88, 95% CI −1.04 to −0.72%, p < 0.00001; Total: SMD −0.66, 95% CI −0.79 to −0.53%, p < 0.00001]. In addition, ipragliflozin as adjuvant therapy to metformin body weight (Total: SMD −1.47, 95% CI [−1.80,-1.14], p < 0.00001), waist circumference (Total: SMD −1.09, 95% CI [−1.62,-0.56], p < 0.00001), and blood pressure (SBP Total: SMD −3.36, 95% CI [−5.11.-1.61], p = 0.0002; DBP Total: SMD −2.18, 95% CI [−3.63,-0.74], p = 0.003). Compared to metformin alone, ipragliflozin as an adjuvant to metformin showed significant risks in the skin and subcutaneous tissue disorders and constipation.

Conclusion: Compared to metformin alone, ipragliflozin plus metformin significantly improved glycemic control, reduced body weight, and lowered blood pressure; however, further high-quality trials are required to determine their long-term efficacy and safety.

KEYWORDS:

• Ipragliflozin
• metformin
• type 2 diabetes mellitus
• SGLT2 inhibitor
• meta-analysis

Acknowledgments

The authors acknowledge the assistance of Ms. Zheng in proofreading the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial relationships to disclose.

Supplementary material

Supplementary material can be accessed here.

Additional information

Funding

The study is supported by Sichuan Science and Technology Program (2016JY0162), Sichuan Applied Basic Research Project (14JC0069) and Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease (xtcx-2016-08), Sichuan, China.