Rationale and design of study of dapagliflozin versus sitagliptin treatment efficacy on prevention of cardiovascular risk factors in type 2 diabetes patients: the DIVERSITY-CVR study.

Background: Recent studies reported that sodium glucose cotransporter 2 (SGLT2) inhibitors reduced the cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM) compared to placebo in contrast to no reduction with dipeptidyl peptidase 4 (DPP4) inhibitors. However, there are no comparative studies on the effects of SGLT2 inhibitors and DPP4 inhibitors on HbA1c, body weight and hypoglycemia as risk factors of cardiovascular diseases. The aim of the present ongoing study is to compare the effects of dapagliflozin, a SGLT2 inhibitor, with those of sitagliptin, a DPP4 inhibitor, on cardiovascular risk factors in T2DM patients with inadequate glycemic control.
Methods: The study of dapagliflozin versus sitagliptin treatment efficacy on prevention of cardiovascular risk factors in T2DM patients (DIVERSITY-CVR study) is a prospective, randomized, open-label, blinded-endpoint, parallel-group, comparative study. A total of 340 T2DM patients treated with metformin alone or with no glucose-lowering agents (hemoglobin A1c ≥ 7.0 and < 10.0%) will be randomized into the dapagliflozin group (5-10 mg/day, n = 170) and the sitagliptin group (50-100 mg/day, n = 170), and treated for 24 weeks. The primary endpoint is the rate of achieving a composite endpoint of the following three items at 24th week; (1) HbA1c < 7.0%; (2) body weight loss of ≥ 3.0% from baseline; (3) avoidance of hypoglycemia. Hypoglycemia will be monitored using the flash glucose monitoring system. The secondary outcomes include each component of the primary endpoint, plus indices of lipid metabolism, and evaluations related to safety.
Conclusions: There is lack of solid information on differences in the therapeutic effects of SGLT2 inhibitors and DPP4 inhibitors on multiple risk factors for cardiovascular diseases. It is anticipated that the results of the DIVERSITY-CVR study provides useful clinical data on the management of patients with T2DM, including reducing the risk of CVD. The results of this study will become available in 2019. Trial registration University Hospital Medical Information Network Clinical Trial Registry (UMIN000028014). Registered 30 June 2017.