PMID- 32370806 OWN - NLM STAT- MEDLINE DCOM- 20210129 LR - 20221207 IS - 1745-6215 (Electronic) IS - 1745-6215 (Linking) VI - 21 IP - 1 DP - 2020 May 5 TI - The effect of luseogliflozin on bone microarchitecture in older patients with type 2 diabetes: study protocol for a randomized controlled pilot trial using second-generation, high-resolution, peripheral quantitative computed tomography (HR-pQCT). PG - 379 LID - 10.1186/s13063-020-04276-4 [doi] LID - 379 AB - BACKGROUND: Older patients with type 2 diabetes mellitus (T2DM) have an increased risk of bone fracture independent of their bone mineral density (BMD), which is explained mainly by the deteriorated bone quality in T2DM compared to that in non-diabetic adults. Sodium-glucose co-transporter (SGLT) 2 inhibitors have been studied in several trials in T2DM, and the Canagliflozin Cardiovascular Assessment Study showed an increased fracture risk related to treatment with the SGLT2 inhibitor canagliflozin, although no evidence of increased fracture risk with treatment with other SGLT2 inhibitors has been reported. The mechanism of the difference in the fracture risk between the SGLT2 inhibitors is unknown, but the differences among the SGLT2 inhibitors in the selectivity of SGLT2 against SGLT1 may affect bone metabolism, since among the SGLT2 inhibitors the selectivity of canagliflozin is lowest. We will investigate whether the SGLT2 inhibitor luseogliflozin, which has the higher SGLT2 selectivity, affects bone metabolism by using high-resolution, peripheral quantitative computed tomography (HR-pQCT) which provides direct in vivo morphometric information about the bone microarchitecture. METHODS/DESIGN: This is a single-center, randomized, open-label, active-controlled, parallel pilot trial. Eligible participants are older (age >/= 60 years) individuals with T2DM with HbA1c levels at 7.0-8.9%. A total of 24 participants will be allocated to either the luseogliflozin group (taking luseogliflozin) or the control group (taking metformin) in a 1:1 ratio to compare the groups' changes in bone microarchitecture of the radius and tibia which are analyzed by HR-pQCT before and at 48 weeks after the administration of each medication. The laboratory data associated with glycemic control and bone metabolism will be collected every 12 weeks during the study. Recruitment began in June 2019. DISCUSSION: The reason that we use metformin as an active control is to avoid yielding differences in glycemic control between the luseogliflozin and control groups. Besides, metformin is considered to have a neutral effect on bone. This trial should reveal the effect of luseogliflozin on bone metabolism in older patients with T2DM. TRIAL REGISTRATION: The study was registered with the University Hospital Medical Information Network (UMIN000036202) on 1 April 2019 and with the Japan Registry of Clinicla Trials (jRCTs071180061) on 14 March 2019. FAU - Haraguchi, Ai AU - Haraguchi A AD - Department of Endocrinology and Metabolism, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. AD - Division of Advanced Preventive Medical Sciences, Department of Endocrinology and Metabolism, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Shigeno, Riyoko AU - Shigeno R AD - Department of Endocrinology and Metabolism, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. AD - Division of Advanced Preventive Medical Sciences, Department of Endocrinology and Metabolism, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Horie, Ichiro AU - Horie I AD - Department of Endocrinology and Metabolism, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. horie@nagasaki-u.ac.jp. AD - Division of Advanced Preventive Medical Sciences, Department of Endocrinology and Metabolism, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. horie@nagasaki-u.ac.jp. FAU - Morimoto, Shimpei AU - Morimoto S AD - Innovation Platform and Office for Precision Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Ito, Ayako AU - Ito A AD - Department of Endocrinology and Metabolism, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. AD - Division of Advanced Preventive Medical Sciences, Department of Endocrinology and Metabolism, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Chiba, Ko AU - Chiba K AD - Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Kawazoe, Yurika AU - Kawazoe Y AD - Clinical Research Center, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Tashiro, Shigeki AU - Tashiro S AD - Clinical Research Center, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Miyamoto, Junya AU - Miyamoto J AD - Clinical Research Center, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Sato, Shuntaro AU - Sato S AD - Clinical Research Center, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Yamamoto, Hiroshi AU - Yamamoto H AD - Clinical Research Center, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Osaki, Makoto AU - Osaki M AD - Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Kawakami, Atsushi AU - Kawakami A AD - Department of Endocrinology and Metabolism, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. AD - Division of Advanced Preventive Medical Sciences, Department of Endocrinology and Metabolism, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Abiru, Norio AU - Abiru N AD - Department of Endocrinology and Metabolism, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. AD - Division of Advanced Preventive Medical Sciences, Department of Endocrinology and Metabolism, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. LA - eng PT - Clinical Trial Protocol PT - Journal Article DEP - 20200505 PL - England TA - Trials JT - Trials JID - 101263253 RN - 0 (Glycated Hemoglobin A) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (hemoglobin A1c protein, human) RN - 506T60A25R (Sorbitol) RN - 9100L32L2N (Metformin) RN - C596HWF74Z (1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol) SB - IM MH - Aged MH - Aged, 80 and over MH - Bone Density/*drug effects MH - Diabetes Mellitus, Type 2/blood/*diagnostic imaging/*drug therapy/epidemiology MH - Female MH - Follow-Up Studies MH - Fractures, Bone/chemically induced MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects MH - Japan/epidemiology MH - Male MH - Metformin/administration & dosage MH - Middle Aged MH - Pilot Projects MH - Randomized Controlled Trials as Topic MH - Risk MH - Sodium-Glucose Transporter 2 Inhibitors/*administration & dosage/adverse effects MH - Sorbitol/administration & dosage/adverse effects/*analogs & derivatives MH - Tomography, X-Ray Computed/*methods PMC - PMC7201752 OTO - NOTNLM OT - Bone OT - Fracture OT - HR-pQCT OT - Luseogliflozin OT - Pilot OT - Randomized controlled trial OT - SGLT2 inhibitor OT - Type 2 diabetes COIS- None declared EDAT- 2020/05/07 06:00 MHDA- 2021/01/30 06:00 PMCR- 2020/05/05 CRDT- 2020/05/07 06:00 PHST- 2019/08/30 00:00 [received] PHST- 2020/03/24 00:00 [accepted] PHST- 2020/05/07 06:00 [entrez] PHST- 2020/05/07 06:00 [pubmed] PHST- 2021/01/30 06:00 [medline] PHST- 2020/05/05 00:00 [pmc-release] AID - 10.1186/s13063-020-04276-4 [pii] AID - 4276 [pii] AID - 10.1186/s13063-020-04276-4 [doi] PST - epublish SO - Trials. 2020 May 5;21(1):379. doi: 10.1186/s13063-020-04276-4.