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

Abstract

BackgroundRecent 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.MethodsThe 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.ConclusionsThere 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 2017Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0730-z) contains supplementary material, which is available to authorized users.

Efficacy of dapagliflozin versus sitagliptin on cardiometabolic risk factors in Japanese patients with type 2 diabetes: a prospective, randomized study (DIVERSITY-CVR)

“…We used data from our previous studies [23,24] to estimate the expected difference in the primary endpoint and determine the required sample size for this study [20]. The details of determining the sample size are described in the previous rationale report of this study [20]. Analyses for the primary and secondary endpoints were primarily performed on the full analysis set (FAS), which included all subjects assigned to a study intervention.…”

“…Specifically, we assessed the success of maintaining HbA1c levels < 7.0% (53 mmol/mol) while avoiding hypoglycemia and achieving adequate body weight reduction. This prospective trial was the first study to clinically evaluate the therapeutic benefits of dapagliflozin and sitagliptin on cardiometabolic risks by focusing concomitantly on achieving target HbA1c level < 7.0% (53 mmol/mol), maintenance of sensor glucose ≥ 3.0 mmol/L or ≥ 54 mg/dL (avoidance of hypoglycemia), and ≥ 3.0% loss of body weight in patients with type 2 diabetes [20]. Notably, hypoglycemia was carefully monitored using a flash glucose monitoring (FGM) system [21].…”

Beneficios de los inhibidores de la dipeptidil peptidasa-4 frente a otros hipoglucemiantes orales

“…12 Los resultados fueron valorados a partir de 24 semanas de pruebas, vigilando a los sujetos de estudio durante todo el proceso para así poder excluir a los pacientes que generaran hipoglucemias, bradicardia y otros efectos cardiovasculares como IAM, EVC, etc. 13 A lo largo del análisis acerca de los hipoglucemiantes orales destaca que, en comparación con las sulfonilureas, incluso en combinación con otras farmacoterapias como las guanidas, los iDPP4, en especial la sitagliptina, han Tabla 4. Inhibidores de DPP4 resultado ser más eficaces en monoterapia, principalmente en pacientes con T2DM descontrolada y en tratamiento con terapias combinadas de biguanidas y sulfonilureas.…”

“…Sin embargo, las ventajas extra glucémicas antes mencionadas sugieren el uso de iDPP4 en mayor medida. 13 Una contraindicación demostrada para el uso de este hipoglicemiante son pacientes con un antecedente de presentar hipoglucemias en repetidas ocasiones siendo o no severas y sintomáticas; esto a pesar de ser un medicamento con bajo riesgo, según lo encontrado en los artículos previamente revisados. 11 Hay que resaltar que la eficacia como monoterapia es significativamente menor que la terapia dual con metformina e iDPP-4, habitualmente sitagliptina.…”

Comparison of the effects of sitagliptin and dapagliflozin on time in range in Japanese patients with type 2 diabetes stratified by body mass index: A sub‐analysis of the DIVERSITY‐CVR study

“…The design, rationale, and primary and secondary outcomes of this study have been previously described. 32…”