Effects of switching from a dipeptidyl peptidase-4 inhibitor to luseogliflozin on nocturnal blood pressure in patients with type 2 diabetes: protocol for a multicentre, prospective, randomised, open-label, blinded endpoint parallel-group comparison study.

Introduction: Nocturnal hypertension is clinically important for patients with type 2 diabetes (T2D), considering its strong correlation with cardiovascular events. We aim to test the hypothesis that the sodium-glucose cotransporter 2 inhibitor, luseogliflozin, ameliorates nocturnal hypertension more effectively than a dipeptidyl peptidase (DPP)-4 inhibitor in patients with T2D.
Methods and Analysis: This study is a multicentre, prospective, randomised, open-label, blinded endpoint parallel-group trial. Sixty participants with T2D and hypertension who have been treated with a DPP-4 inhibitor for more than 4 weeks and who have a glycated haemoglobin A1c (HbA1c) level of 6.0%-9.0% will be randomised based on age, body mass index (BMI) and HbA1c to continue taking their DPP-4 inhibitor or to switch to luseogliflozin 2.5 mg once daily for 8 weeks. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) will be performed twice at baseline and at the end of the study. All participants will continue their diet and exercise therapy, and the doses of concomitant medications will not be adjusted during the study. The primary endpoint is the effect of luseogliflozin on the mean change in systolic blood pressure (SBP) during the night, as measured by ABPM. The secondary endpoints are mean change in diastolic blood pressure (DBP) during the night, 24 hours of SBP and DBP, daytime SBP and DBP, pulse rate, BP M-value, trough SBP and DBP for 1 hour before the next dose, and other laboratory parameters. The sample size was calculated for a two-sided test at 90% power for the detection of a difference between treatments.
Ethics and Dissemination: The Ethics Review Board of Hokkaido University Hospital has approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences.
Trial Registration Numbers: The University Hospital Medical Information Network (UMIN000031451); Japan Registry of Clinical Trials (jRCTs011180019); Pre-results.
Competing Interests: Competing interests: AN has received honoraria for lectures from Sanofi, Mitsubishi Tanabe Pharma, Daiichi Sankyo, Eli Lilly Japan, MSD, Novo Nordisk Pharma, Novartis Pharma, AstraZeneca, Takeda Pharmaceutical, Astellas, Kowa Pharmaceutical, Ono, Nippon Boehringer Ingelheim, and Taisho Toyama Pharmaceutical, and has obtained research support from Mitsubishi Tanabe Pharma, Daiichi Sankyo, MSD, Novo Nordisk Pharma, Novartis Pharma, AstraZeneca, Dainippon Sumitomo Pharma, Life Scan Japan, and Taisho Pharmaceutical Co., Ltd. YK has received honoraria for lectures from Astellas Pharma Inc., AstraZeneca, Mitsubishi Tanabe Pharma Co., Ltd., MSD, Ono Pharmaceutical Co., Ltd., Sanofi, Shionogi & Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd. TA has received honoraria for lectures from Mitsubishi Tanabe Pharma, Chugai Pharmaceutical, Astellas Pharma, Takeda Pharmaceutical, Pfizer, and Eli Lilly, and has received research funding from Astellas Pharma, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, Chugai Pharmaceutical, Daiichi Sankyo, and Otsuka Pharmaceutical. HM has received honoraria for lectures from Astellas Pharma, AstraZeneca, Dainippon Pharma, Eli Lilly, Kissei, Mitsubishi Tanabe Pharma, MSD, Novo Nordisk Pharma, Novartis Pharma, and Sanofi, and has received research funding from Astellas Pharma, Astra‐Zeneca, Eli Lilly, and Mitsubishi Tanabe Pharma.
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