UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000014140
Receipt number R000016469
Scientific Title Efficacy and Safety of GLP-1 first therapy compared with Insulin GLP-1 relay therapy in type 2 diabetes with inadequate glucose control: a randomized, open-label, multicenter parallel-group study
Date of disclosure of the study information 2014/06/02
Last modified on 2021/12/10 09:49:59

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Basic information

Public title

Efficacy and Safety of GLP-1 first therapy compared with Insulin GLP-1 relay therapy in type 2 diabetes with inadequate glucose control: a randomized, open-label, multicenter parallel-group study

Acronym

Direct comparison of GLP-1 first therapy and Insulin-GLP-1 relay therapy.

Scientific Title

Efficacy and Safety of GLP-1 first therapy compared with Insulin GLP-1 relay therapy in type 2 diabetes with inadequate glucose control: a randomized, open-label, multicenter parallel-group study

Scientific Title:Acronym

Direct comparison of GLP-1 first therapy and Insulin-GLP-1 relay therapy.

Region

Japan


Condition

Condition

Type 2 diabetes

Classification by specialty

Medicine in general Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

To confirm efficacy and safety of GLP-1 first therapy and Insulin GLP-1 relay therapy in type 2 diabetes with inadequate glucose control as introduction of injectable medicine.

Basic objectives2

Safety,Efficacy

Basic objectives -Others


Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable


Assessment

Primary outcomes

Blood glucose control by change in FPG, 1,5-AG and HbA1c.
Achievement rate of HbA1c goals below 7%.

Key secondary outcomes

1 Change in physical findings by change of body weight, adipose mass, basal metabolism and waist circumference
2 Change in biochemical finding
3 Change in lipid metabolism (TC, HDL-C, TG)
Change in hepatic and renal function
4 Identification of predictors for improvement of glucose control
5 Upper limit of daily insulin dose which can be changed from insulin therapy to GLP-1 therapy
6 Adverse events
7 Change in hepatokine


Base

Study type

Interventional


Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Cluster

Blinding

Open -no one is blinded

Control

Active

Stratification


Dynamic allocation


Institution consideration


Blocking


Concealment

Central registration


Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

GLP-1 first therapy
Liraglutide (6 months)

Interventions/Control_2

Insulin GLP-1 relay therapy
Insulin degludec from baseline to 3 month (3 months)
Liraglutide from 4 to 6 month (3 months)

Interventions/Control_3


Interventions/Control_4


Interventions/Control_5


Interventions/Control_6


Interventions/Control_7


Interventions/Control_8


Interventions/Control_9


Interventions/Control_10



Eligibility

Age-lower limit

20 years-old <=

Age-upper limit


Not applicable

Gender

Male and Female

Key inclusion criteria

Type 2 diabetes with HbA1c above 8%
No limitation in sex and in or out-patients.

Key exclusion criteria

Patients who have history of serious hypersensitivity to Liraglutide, Exenatide, Lixisenatide and insulin degludec.
Patients with type 1 diabetes or impaired glucose tolerance due to other specific mechanisms or diseases or gestational diabetes.
Patients with diabetic ketoacidosis
Patients who have history of severe hypoglycemia with coma or loss of consciousness
Patients with serious infection or severe traumatic injury
Patients with steroids as unstable daily dose.
Patients with unstable hypertension with medication like systolic blood pressure above 160 mmHg or diastolic blood pressure above 100mmHg.
Patients with severe hepatic failure or renal failure or cardiac disorder and identified inappropriate patients for this study by the physicians in charge.
Patients with proliferative retinopathy (excluding old proliferative retinopathy without necessary of intervention) and patients with maculopathy with necessary of intervention.
Patients who have history of malignancy
Excluding following patients
Patients who have history of cured basal cell tumor by appropriate treatment or uterocervical carcinoma in situ
Patients who have history of malignancy more than 1 year before and also have no reappearance
Patients who onset malignancy during the period of the study.
Patients with severe complication and identified inappropriate patients for this study by the physicians in charge.
The pregnant women or women having possibilities of being pregnant and the women with breast-feeding
Other patients who are identified inappropriate patients for this study by the physicians in charge.

Target sample size

120


Research contact person

Name of lead principal investigator

1st name Toshinari
Middle name
Last name Takamura

Organization

Kanazawa university

Division name

Department of Disease Control and Homeostasis

Zip code

920-8641

Address

13-1, Takara-cho, Kanazawa-shi, Kanazawa, 920-8641 Japan

TEL

076-265-2234

Email

ttakamura@m-kanazawa.jp


Public contact

Name of contact person

1st name Toshinari
Middle name
Last name Takamura

Organization

Kanazawa university

Division name

Department of Disease Control and Homeostasis

Zip code

920-8641

Address

13-1, Takara-cho, Kanazawa-shi, Kanazawa, 920-8641 Japan

TEL

076-265-2234

Homepage URL


Email

ttakamura@m-kanazawa.jp


Sponsor or person

Institute

Kanazawa university
Department of Disease Control and Homeostasis

Institute

Department

Personal name



Funding Source

Organization

Kanazawa university
Department of Disease Control and Homeostasis

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization



Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization

Innovative Clinical Research Center, Kanazawa University.

Address

13-1, Takara-cho, Kanazawa-shi, Kanazawa, 920-8641 Japan

Tel

076-265-2049

Email

rinri@adm.kanazawa-u.ac.jp


Secondary IDs

Secondary IDs

NO

Study ID_1


Org. issuing International ID_1


Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions



Other administrative information

Date of disclosure of the study information

2014 Year 06 Month 02 Day


Related information

URL releasing protocol

https://kanazawa.esct.jp/kurea/Common/

Publication of results

Unpublished


Result

URL related to results and publications

https://kanazawa.esct.jp/kurea/Common/

Number of participants that the trial has enrolled

120

Results

The GLP-1 receptor agonist is overall effective without prior glycemic control with insulin in participants with poorly controlled type 2 diabetes. However, in participants with insulinopenic type 2 diabetes, prior glycemic control with insulin may overcome glucose toxicity-induced GLP-1 resistance.

Results date posted

2021 Year 12 Month 10 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics

The median age of the participants in FAS was 61.0 years BMI 25.8 diabetes duration 4.0 years and baseline levels for FPG, HbA1c, and CPR 210.0 mg/dl 9.8%, and 2.2 ng/mL, respectively. Microalbuminuria was present in 17 out of 116 for this study. No study participant experienced macroalbuminuria. As the percentage of newly diagnosed with diabetes is 33.6% of this study, the participants have no or mild diabetic complications such as diabetic nephropathy.

Participant flow

In total, 120 individuals participated in the study (n = 60 in the insulin-GLP-1 RA relay group, n = 60 in the GLP-1 RA first group). Of these, 91 took the study medication up to week 24, whereas 13 discontinued it due to an adverse event (n = 7 in the insulin-GLP-1 RA relay group, n = 2 in the GLP-1 RA first group) or withdrew participation (n = 3 in the insulin-GLP-1 RA relay group, n = 1 in the GLP-1 RA first group). During follow-up, 12 were lost (n = 3 in the insulin-GLP-1 RA relay group, n = 9 in the GLP-1 RA first group).

Adverse events

Concerning adverse events, gastrointestinal issues such as nausea, abdominal distension, constipation, and diarrhea were the most common and occurred more frequently in the GLP-1 RA first group than in the insulin-GLP-1 RA relay group, followed by hypoglycemia in the insulin GLP1 RA relay group.

Outcome measures

At 24 weeks, the FPG levels significantly decreased from baseline for the insulin-GLP-1 RA relay group (215.0 to 126.0 mg/dL, ) and GLP-1 RA first group (204.0 to 131.5 mg/dL), with no significant differences between groups (-68.0 mg/dL in the insulin-GLP-1 RA relay group, -43.0 mg/dL in the GLP-1 RA first group, p = 0.155). Similarly, the HbA1c levels significantly decreased from baseline for the insulin-GLP-1 RA relay group (9.8% to 6.5%) and the GLP-1 RA first group (9.7% to 6.8%), with no significant differences between groups (-2.8% in the insulin-GLP-1 RA relay group, -2.1% in the GLP-1 RA first group, p = 0.286). The differences between the groups for these primary clinical outcomes were unremarkable.

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2014 Year 06 Month 02 Day

Date of IRB

2013 Year 04 Month 16 Day

Anticipated trial start date

2014 Year 06 Month 02 Day

Last follow-up date

2019 Year 05 Month 30 Day

Date of closure to data entry

2019 Year 12 Month 31 Day

Date trial data considered complete

2019 Year 12 Month 31 Day

Date analysis concluded



Other

Other related information



Management information

Registered date

2014 Year 06 Month 02 Day

Last modified on

2021 Year 12 Month 10 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000016469


Research Plan
Registered date File name
2017/12/05 140718-ノボIRB研究計画.doc

Research case data specifications
Registered date File name

Research case data
Registered date File name