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

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.