An Exploratory Study of Dapagliflozin for the Attenuation of Albuminuria in Patients with Heart Failure and Type 2 Diabetes Mellitus (DAPPER)
Background and Aims
Sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, which are anti-diabetic drugs, reportedly decrease the incidence of cardiovascular events in high-risk patients with cardiovascular diseases, and thus chronic heart failure (CHF). SGLT-2 inhibitors also decrease albuminuria in patients with type 2 diabetes mellitus (T2D). Since albuminuria is a biomarker of not only chronic kidney disease but also cardiovascular events, we hypothesized that, among T2D patients with CHF, SGLT-2 inhibitors will decrease the extent of albuminuria and also improve CHF concomitantly.
DAPPER (UMIN000025102) is a multicenter, randomized, open-labeled, parallel-group, standard treatment-controlled study, which is designed to evaluate whether dapagliflozin, one of the SGLT-2 inhibitors, decreases albuminuria in T2D patients with CHF and exerts cardioprotective effects on the failing heart. The patients are randomized to either of the dapagliflozin (5 or 10 mg, once daily orally) or control group (administration of anti-diabetic drugs administered other than SGLT 2 inhibitors). The estimated number of patients that need to be enrolled is 446 in total (223 in each group). The primary objective is the changes in the urinary albumin-to-creatinine ratio from the baseline after 2-year treatment. The key secondary objectives are (1) the safety of dapagliflozin and (2) the cardiovascular and renal efficacies of dapagliflozin.
Conclusion and Perspectives
DAPPER study investigates whether dapagliflozin decreases albuminuria and exerts beneficial effects on the failing heart in T2D patients. (UMIN000025102).
KeywordsDapagliflozin Type 2 diabetes mellitus Chronic heart failure Urinary albumin-to-creatinine ratio Cardiovascular protection
We acknowledge the great help from Ms. T. Takahashi, R. Umezawa, M. Saida, and M. Yoda for their secretarial assistance.
MK conceived of the study and FY, TH, MK wrote the manuscript. MI, SI, KH, YY, KM, MW, and MA conceived of and coordinated the study. TH and HY performed statistical analyses and provided the biostatistical study design. SY and TA conceived of and supervised the study. MK conceived of and supervised the study and is the grant holder. All authors read and approved the final manuscript.
Compliance with Ethical Standards
Conflict of Interest
FY and MK report grants and personal fees from AstraZeneca Plc. and Ono Pharmaceutical Co., LTD, during the conduct of the study.
FY also receive grants from the Japanese government (KAKENHI-PROJECT-17K09002), personal fees from Otsuka, personal fees from Chugai, personal fees from Kyowa-Hakko-Kirin, personal fees from Pfizer, personal fees from Boehringer Ingelheim, personal fees from Novo Nordisk, personal fees from Daiichi Sankyo, personal fees from Takeda, personal fees from AstraZeneca, personal fees from Sumitomo Dainippon, outside the submitted work.
MK also receive grants from the Japanese government (KAKENHI-PROJECT-15H04826), grants from Japan Heart Foundation, grants from Japan Cardiovascular Research Foundation, grants and personal fees from Asteras, grants and personal fees from Sanofi, personal fees from Daiichi Sankyo, grants and personal fees from Pfizer, grants and personal fees from Ono, personal fees from Bayer, grants from Novartis, personal fees from Bheringer, grants and personal fees from Tanabe-mitsubishi, personal fees from Kowa, personal fees from Dainihon-sumitomo, personal fees from Sawai, personal fees from MSD, grants and personal fees from Otsuka, grants from Nihon Kohden, personal fees from Shionogi, grants and personal fees from Astrazeneca, grants and personal fees from Takeda, from Taisho-toyama, outside the submitted work.
MI has nothing to disclose.
TH has nothing to disclose.
TA has nothing to disclose.
SY has nothing to disclose.
SI has nothing to disclose.
HY has nothing to disclose.
KH has nothing to disclose.
YY has nothing to disclose.
KM reports grants from Mitsubishi Tanabe Pharma Corporation, grants and personal fees from Abbott Japan, outside the submitted work.
MW has nothing to disclose.
MA reports grants from Acterion Pharmaceutical Japan, grants from Boehringer Ingelheim Japan, Inc., personal fees from Otsuka Pharmaceutical Co., Ltd., personal fees from Sanofi K.K., personal fees from Bayer Yakuhin, Ltd., personal fees from MSD K.K., personal fees from Takeda Pharmaceutical Company Limited., personal fees from Pfizer Japan Inc., outside the submitted work.
Ethics Approval and Consent to Participate
The final protocol was approved by the National Cerebral and Cardiovascular Center Ethics Committee (approval ID M28-059) and each Institutional Review Board of all participating centers and patient enrollment began in April 2017. This study complies with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Written informed consent will be obtained from all patients before recruitment. Personal information about potential and enrolled participants will remain confidential and data will be never identified using participant’s number. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000025102 (http://www.umin.ac.jp/ctr/index-j.htm).
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