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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
(Bone microstructural changes under luseogliflozin treatment)

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
(Bone microstructural changes under luseogliflozin treatment)

22

The total 22 subjects (female, 32%) were randomly assigned to either the Lusefi group which was administered luseogliflozin 2.5mg (n=10) or the Control group which was administered metformin 500mg(n=12). The mean age of the Lusefi group was 69.4 years and that of the Control group was 67.7 years. The mean BMI of the Lusefi group was 26.1 kg/m2 and that of the Control group was 23.4 kg/m2.

Patients had been enrolled from April 2019 to December 2021. Of the 22 subjects (10 in the Lusefi group and 12 in the Control group),20 subjects (9 in the Lusefi group and 11 in the Control group) had completed the study.

One male patient in the Control group developed atrial fibrillation and received oral treatment. One woman allocated to the Control group withdraw from the study because of hospitalization due to coronavirus disease 2019(COVID-19). One man allocated to the Lusefi group withdraw from the study because he died suffering from acute cardioembolic stroke. However, the adverse events in both any patients were not confirmed being related with the research drugs. Additionally, one female patient in the Lusefi group developed cystitis, which improved with oral antibiotics, but the association with the research drug was unlikely.

Primary outcome: The 48 weeks changes in the micro FE-estimated stiffness and failure load calculated by HR-pQCT showed no significant differences between the Lusefi group and the Control group. Secondary outcome: There were no fracture events occurred during the study period. The 48 weeks changes in the bone mineral density of lumbar spine, femur, and radius by DXA showed no significant differences between the two groups. The 48 weeks changes in all bone parameters measured by HR-pQCT showed no significant differences between the two groups. In the Lusefi group, the mean levels of hematocrit, hemoglobin and red blood cells significantly increased, and those of systolic blood pressure and uric acid significantly decreased from baseline to Week 48, compared to the Control group. No significant differences were observed in the 48 weeks changes in the serum bone metabolic markers between the two groups.

No adverse effectes on bone microarchitecture were observed by 48 weeks treatment with luseogliflozin in patients with type 2 diabetes.

Dec. 01, 2024

No

use identigication nuber

https://jrct.mhlw.go.jp/latest-detail/jRCTs071180061

Horie Ichiro

Nagasaki University Hospital

1-7-1 Sakamoto, Nagasaki

holy197741@me.com

Horie Ichiro

Nagasaki University Hospital

1-7-1 Sakamoto, Nagasaki

+81-95-819-7200

holy197741@me.com

Complete

April. 01, 2019

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

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.

(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.

Both

Type 2 diabetes

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.

Changes in the predicted bone strength of radius and tibia calculated using HR-pQCT

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

+81-95-819-7905

Mar. 14, 2019

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