Study limitations
TYPE 2 DIABETES
This study has some limitations. First, the number of subjects in the present study, as a sub-analysis of the PROTECT trial, was relatively small. Because FMD was an optional measurement in the PROTECT trial, there was an insufficient sample size for power calculation, and the analysis may have been underpowered. However, the results of analysis of the PROTECT trial, a multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, provide valuable information that may help us to understand the impact of ipragliflozin on endothelial function in patients with type 2 diabetes. Further studies with a larger number of participants are required to validate the long-term impacts of SGLT2 inhibitors on endothelial function in patients with type 2 diabetes. Second, LDL cholesterol levels in the control group after 24 months were significantly lower than those in the ipragliflozin group after 24 months, although there was no change in the use of dyslipidemia-improving drugs, including statins, ezetimibe, fibrates, and eicosapentaenoic acid, in either group. Lowering LDL cholesterol levels improves vascular endothelial function. The lower LDL cholesterol level in the control group at 24 months may have been one reason for the lack of a significant difference in FMD between the two groups. However, there was no significant difference in FMD between the two groups after adjusting for LDL cholesterol.