UMIN-ICDS Clinical Trial

Public title

Study on the glucose-lowering effect and metabolic benefit of SGLT2 inhibitors

Acronym

Study on the glucose-lowering effect and metabolic benefit of SGLT2 inhibitors

Scientific Title

Prospective observational study on metabolic changes induced by SGLT2 inhibitors or insulin treatment in a single-center, two-arm, open-label design

Scientific Title:Acronym

prospective observational study on metabolic changes induced by SGLT2 inhibitors or insulin treatment

Region

Japan

Condition

Diabetes mellitus

Classification by specialty

Endocrinology and Metabolism

Adult

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To elucidate the glucose-lowering effect and metabolic benefit of SGLT2 inhibitors.

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Changes in the levels of HbA1c.

Key secondary outcomes

Changes in the levels of glycated albumin, fasting blood glucose, and urinary albumin/creatinine ratio.

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

80

years-old

>

Gender

Male and Female

Key inclusion criteria

Inclusion criteria comprised a diagnosis of type 2 diabetes mellitus with HbA1c 6.5% or more, age between 20 and 79 years, a stable antidiabetic regimen with insulin for at least 8 weeks prior to the study, and no prior use of SGLT2 inhibitors.

Key exclusion criteria

Exclusion criteria encompassed pregnant or breastfeeding women, patients with malignant disease, severe infections (including urinary tract infections), severe trauma, or recent surgery.

Target sample size

60

Name of lead principal investigator

1st name	Moeko
Middle name
Last name	Sakamoto

Organization

Department of Internal Medicine, Kurume University School of Medicine

Division name

Division of Endocrinology and Metabolism

Zip code

830-0011

Address

67 Asahi-machi, Kurume-shi, Fukuoka, Japan

TEL

0942-31-7563

Email

matsumoto_moeko@kurume-u.ac.jp

Name of contact person

1st name	Moeko
Middle name
Last name	Sakamoto

Organization

Department of Internal Medicine, Kurume University School of Medicine

Division name

Division of Endocrinology and Metabolism

Zip code

830-0011

Address

67 Asahi-machi, Kurume-shi, Fukuoka, Japan

TEL

0942-31-7563

Homepage URL

Email

matsumoto_moeko@kurume-u.ac.jp

Institute

Department of Internal Medicine, Kurume University School of Medicine

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Ethics Committee of Kurume University School of Medicine

Address

67 Asahi-machi, Kurume-shi, Fukuoka, Japan

Tel

0942-31-7563

Email

i_rinri@kurume-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2023

Year

11

Month

30

Day

URL releasing protocol

None

Publication of results

Unpublished

URL related to results and publications

None

Number of participants that the trial has enrolled

17

Results

The intervention did not induce significant differences in HbA1c between the groups. The dapagliflozin group showed a significant decrease in body fat mass and percentage, along with an increase in skeletal muscle percentage. Among analyzed the 10 urinary biomarkers of diabetic kidney disease, only 3OH propionic acid showed a significant increase in the dapagliflozin-treated group compared to the insulin-treated group, suggesting that dapagliflozin modulates BCAA metabolism primarily in the kidney.

Results date posted

2023

Year

11

Month

30

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

insulin group　　　　
N 　　　　　　　　 5 women3men2
Age years 　　　　　　　　72.2
Weight kg 　　　　　　　　66.8
Body mass index kg/m2 24.9
FPG mg/dl　 　　　　　　　142.2
HbA1c mmol/mol 　　　　　　　　7.6
Estimated GFR mL/min/1.73 m2 59.3
U-albmin mg/g Cre 　　　　401.2


dapagliflozin group
N women/men 　　 　　　　8 women2men6
Age years 　　　　　　　　62.0
Weight kg 　　　　　　　　62.2
Body mass index kg/m2 25.2
FPG mg/dl　 　　　　　　　151.1
HbA1c mmol/mol 　　　　　　　7.4
Estimated GFR mL/min/1.73 m2 78.2
U-albmin mg/g Cre 　　　　93.6

Participant flow

A total of seventeen patients were enrolled in the study, with eight assigned to the insulin group and nine to the dapagliflozin group. During the intervention period, three patients in the insulin group withdrew from the study due to the development of malignant disease (n=2) or heart failure (n=1), while one patient in the dapagliflozin group withdrew due to increased urine output (n=1) . Five participants in the insulin group and eight in the dapagliflozin group completed the full 12-week intervention.

Adverse events

Only one patient experienced an increase in urine output that was difficult to continue with dapagliflozin administration.

Outcome measures

The 12-week intervention did not induce significant changes in glycemic control in either group, nor were there significant differences observed between the groups . This can be attributed to the mild increase in insulin dose (2-4 units/day) in the insulin group and the reduction of insulin dose in the dapagliflozin group. In the insulin group, there were no significant changes in body weight, skeletal muscle mass or percentage, or body fat. In contrast, the dapagliflozin group showed a tendency towards decreased body weight and a significant decrease in body fat mass and percentage, along with an increase in skeletal muscle percentage (Table 2). These findings align with our previous study, which demonstrated that long-term treatment with SGLT2 inhibitors over a 2-year period resulted in significant reductions in body fat without affecting skeletal muscle mass26. Renal function markers, including urinary albumin levels and liver-type fatty acid-binding protein (LFABP), did not show significant changes in either group, except for a small increase in estimated glomerular filtration rate (eGFR) in the insulin group.We analyzed the 13 urinary biomarkers of diabetic kidney disease in these patients, and 10 metabolites were detected. Among them, only 3OH propionic acid showed a significant increase in the dapagliflozin-treated group compared to the insulin-treated group (p=0.0493)

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2020

Year

04

Month

23

Day

Date of IRB

2020

Year

05

Month

18

Day

Anticipated trial start date

2020

Year

08

Month

05

Day

Last follow-up date

2022

Year

10

Month

01

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

metabolic changes induced by SGLT2 inhibitors or insulin treatment, prospective study, sampling with non randomized controlled trial

Registered date

2023

Year

11

Month

30

Day

Last modified on

2023

Year

11

Month

30

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000060252