OBJECTIVES : To conduct a systematic literature review (SLR) and target literature review (TLR) of clinical studies on type 2 diabetes (T2D) treatment in Japan and assess various efficacy outcomes such as blood glucose, blood pressure, body weight, kidney function, adherence and Quality of Life, with identification of evidence gaps for future study.

METHODS : SLR and TLR on inadequately controlled T2D patients in Japan were conducted using PubMed and Ichushi DB (for Japanese literature) from 2010 to 2019, based on PICOS. The study protocol was registered to PROSPERO, and we assessed literature by categorizing the outcomes from randomized clinical trials (RCT) and non-RCT including observational studies (non-RCT).

RESULTS : Total 2,694 articles were reviewed, of which 146 articles were finally extracted. Most literature reported change of HbA1c and fasting blood glucose levels, body weight, and blood cholesterol levels associated with treatment, and some literature identified by TLR reported QOL. HbA1c value was used as endpoint in most studies in both RCT and non-RCT, followed by fasting blood glucose, and postprandial glucose level was assessed in some studies. Statistically significant improvement of these efficacy outcomes was observed more in non-RCT than RCT. For treatment regimen, DPP-4 inhibitors were most commonly assessed in RCT, with increasing assessment of glinides from 2014 to 2015 and basal insulin from 2017 to 2018. On the other hand, DPP-4 inhibitors and SGLT-2 inhibitors were most commonly assessed in non-RCT from 2013 to 2014.

CONCLUSIONS : Most literature assessed HbA1c and fasting blood glucose but few assessed adherence and QOL, which are important to manage chronic diseases such as inadequately controlled T2D. Moreover, treatment regimen other than basal insulin, DPP-4, and SGLT-2 were not much reported, limiting further assessment among different regimens. This suggests data gap and future needs to include more patient-related outcomes in addition to clinical outcomes.