Adverse Drug Events Observed with the Novel Sodium/Glucose Co-Transporter 2 Inhibitor Ipragliflozin for the Treatment of Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Studies.

Abstract

Type 2 diabetes mellitus (T2DM) is becoming a major issue worldwide. To effectively control the blood sugar of patients with T2DM, several novel oral hypoglycemic agents (OHAs) are being developed. Sodium/glucose co-transporter 2 (SGLT 2) inhibitors have recently shown beneficial outcomes in patients with T2DM. In this analysis, we aimed to systematically compare the adverse drug events observed with ipragliflozin versus placebo for the treatment of patients with T2DM. http://www.ClinicalTrials.gov , the bibliographic database of life science and biomedical information MEDLINE, EMBASE and the Cochrane Central were searched for English publications satisfying the inclusion and exclusion criteria of this study. Adverse drug events were the end points in this analysis. The latest version (5.4) of the RevMan software was used to analyze the data, and risk ratios (RR) with 95% confidence intervals (CI) were used to represent the data post analysis. Eight randomized studies with a total of 1519 participants with T2DM were included in this analysis whereby total treatment-emergent adverse events (RR: 1.06, 95% CI: 0.96-1.16; P = 0.26), including mild (RR: 0.95, 95% CI: 0.79-1.13; P = 0.54), moderate (RR: 1.04, 95% CI: 0.72-1.51; P = 0.83) and severe treatment-emergent adverse events (RR: 0.72, 95% CI: 0.26-1.96; P = 0.52), were not significantly different in those patients who were assigned to ipragliflozin versus placebo for the treatment of T2DM. Moreover, drug-related adverse events (RR: 1.04, 95% CI: 0.69-1.58; P = 0.85), adverse events leading to drug discontinuation (RR: 1.09, 95% CI: 0.57-2.10; P = 0.79), urinary tract infection (RR: 1.03, 95% CI: 0.60-1.77; P = 0.91), naso-pharyngitis (RR: 0.54, 95% CI: 0.19-1.52; P = 0.25), constipation (RR: 1.94, 95% CI: 0.90-4.20; P = 0.09), dizziness (RR: 0.81, 95% CI: 0.20-3.23; P = 0.76), gastrointestinal disorders (RR: 0.96, 95% CI: 0.68-1.36; P = 0.82) and dehydration (RR: 2.26, 95% CI: 0.38-13.43; P = 0.37) were also not significantly different. However, genital infection (RR: 4.53, 95% CI: 1.48-13.85; P = 0.008) and hypoglycemia (RR: 1.68, 95% CI: 1.03-2.74; P = 0.04) rates were significantly higher in the ipragliflozin group. The current analysis showed ipragliflozin to be associated with significantly higher genital infection rates compared to placebo, whereas no significant difference was observed compared to the other adverse drug events in these patients with T2DM. In addition, hypoglycemia was also not significantly different following sensitivity analysis.