Longitudinal analysis of bone microstructural changes under luseogliflozin treatment using second-generation High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) in elderly patients with type 2 diabetes

JRCT ID: jRCTs071180061

Registered date:19/03/2019

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Type 2 diabetes
• Date of first enrollment: 18/07/2019
• Target sample size: 24
• Study type: Interventional

Intervention(s)

The luseogliflozin group: Administer luseogliflozin 2.5 mg a day orally.
Administration of luseogliflozin is increased to 5.0 mg if participants cannot achieve the HbA1c levels less than 7.0 % at each visit of 12, 24, 36 weeks of the study, or a decrease in the HbA1c of more than or equal to 0.5 % compared with those in the previous visit. Maximum dose of luseogliflozin is permitted up to 5.0 mg per day. If participants cannot achieve the HbA1c levels described above, 500 mg of metformin is added in each visit. However, the dosage increase of metformin is permitted by every 250 mg if the participant is already administered metformin more than or equal to 1500 mg per day. Maximum dose of metformin is permitted up to 2250 mg per day.

The metformin group: Administer metformin 500 mg a day orally in addition to the baseline regime.
Administration of metformin is increased by every 500 mg if participants cannot achieve the HbA1c levels less than 7.0 % at each visit of 12, 24, 36 weeks of the study or a decrease in the HbA1c of more than or equal to 0.5 % compared with those in the previous visit. However, the increase of metformin is permitted by every 250 mg if the participant is already administered metformin more than or equal to 1500 mg per day. Maximum dose of metformin is permitted up to 2250 mg per day.

Outcome(s)

• Primary Outcome: Changes in the predicted bone strength of radius and tibia calculated using HR-pQCT

Secondary Outcome

Changes in the values of blood and biochemical tests;
Changes in the bone mineral density at lumbar spine, femur, radius measured by dual-energy X-ray absorptiometry;
Incidence of vertebral fracture or femoral fracture;
Changes in the values of bone metabolic markers;
Changes in the values related with cortical bone structure, travecular bone structure or bone morphology calculated using by HR-pQCT

Key inclusion & exclusion criteria

• Age minimum: >= 60age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Selection criteria at enrollment into the study
(1) Outpatient
(2) Patient treated with diet therapy alone or with oral anti-diabetic agents including metformin (less than or equal to 1000 mg per day) or/and alpha-glucosidase inhibitors or/and DPP4 inhibitors. The treatment of oral anti-diabetic agents is needed to be not changed within 6 months before enrolled. Patients who have previously treated any anti-diabetic agents excluding metformin, alpha-glucosidase inhibitors, or DPP4 inhibitors can be participated in this study if the treatment was discontinued more than 6 months before enrolled into the study.
(3) Written informed consent

2. Selection criteria at the start of the study
(4) HbA1c level at more than or equal to 7%, and less than 9%.
(5) T-scores of bone mineral density of both lumbar vertebrae and proximal part of femur are over -2.5 S.D. determined by dual energy X-ray absorptiometry.

Exclude criteria

(1) Previous history of treatment with SGLT2 inhibitors
(2) Complicated with bone metabolic disorders including osteomalacia, thyroid dysfunction, hyperparathyroidism or hypoparathyroidism that require any medical treatments
(3) Administered any treatments for osteoporosis described below at present or within the past 12 months before enrolled into the study; bisphosphonate, vitamin D preparation, vitamin K2 preparation, calcium preparation, selective estrogen receptor modulator (SERM), anti-RANKL antibody (denosumab), anti-sclerostin antibody (romosozumab) or parathyroid hormone (teriparatide)
(4) Treated with estrogen or testosterone
(5) Complicated with diabetic retinopathy or/and diabetic neuropathy requiring therapeutic intervention
(6) Sever renal dysfunction with eGFR <30 ml/min/1.73 m2
(7) Anemia with hemoglobin level under 10 g/dL
(8) Complicated with malignancy
(9) Hypersensitivity or allergy to the study drugs including luseogliflozin or metformin
(10) Taking alcohol more than 20 g/day
(11) Smoking cigarette within one year before enrolled into the study
(12) Participated in other clinical trials within 6 months before enrolled into the study
(13) Complicated with chronic liver disease with Child-Pugh score of more than or equal to 6 points.
(14) BMI <18.5 kg/m2
(15) Judged as an unsuitable participant by the researchers.

Related Information

• Primary Sponsor: Horie Ichiro
• Secondary Sponsor: Kawakami Atsushi
• Source(s) of Monetary Support: Taisho Pharmaceutical Co., Ltd.