Safety profiles of sodium-glucose co-transporter 2 inhibitors in Japanese patients with diabetes mellitus: A literature review and meta-analysis

We conducted a literature review and meta-analysis of safety profiles of sodium-glucose co-transporter 2 (SGLT2) inhibitors in Japanese patients with diabetes mellitus (DM). The electronic databases MEDLINE, CENTRAL, and Ichushi-web were searched for studies from their inception through to August 2019 and there was no language restriction. Trials were included in the analysis if they were randomized controlled trials (RCTs) (1) comparing the effects of SGLT2 inhibitors with a placebo in Japanese patients with DM ≤ 18 years, and (2) reporting HbA1c and at least one adverse event. We calculated risk ratios with 95%CI and used a random-effects model. Twenty-two out of the 765 RCTs retrieved were ultimately included in the present review, and only one RCT included patients with type 1 DM. The durations of RCTs ranged between 4 and 24 weeks. In comparisons with a placebo, SGLT2 inhibitors were associated with similar risks of hypoglycemia, urinary tract infection, genital infection, hypovolemia, and fracture. The outcomes of treatments with SGLT2 inhibitors among Japanese patients with DM suggest favorable safety profiles. However, further evidence from studies with a longer duration, involving more diverse populations, or including individual SGLT2 inhibitors is needed to resolve the limitations of the present study.