Clinical trial NCT00736515: Study of Combination Therapy of Gliclazide MR and Basal Insulin Versus Insulin Monotherapy to Treat Type 2 Diabetes
Official title: Phase 4 Study of Comparison of Combination Therapy of Gliclazide MR and Basal Insulin With Pre-mix Insulin Monotherapy for the Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Keywords: combination therapy,monotherapy,gliclazide MR,insulin,CGMS
Lead sponsor: Servier (Tianjin) Pharmaceutical Co. LTD.
Sponsor class: INDUSTRY
First posted: 2008-08-18
Enrollment: 160
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In recent years, with the further research of the pathogenesis of diabetes mellitus and the mechanism of oral antidiabetes drugs, the early combination therapy of oral antidiabetes drugs and insulin is getting paid more and more attention. A lot of studies have confirmed that Gliclazide MRs have excellent reducing blood glucose efficacy and vascular protection. Based on these theory and practice, this study is designed to demonstrate whether the combination therapy of Gliclazide MR and basal insulin can control the blood glycemia effectively and reduce the dosage of insulin and the hypoglycemia events compared to the premix insulin monotherapy.

Detailed description: Inclusion criteria:

1. Male or female with type 2 diabetes mellitus
2. 35 years old≤age≤65 years old
3. 19kg/m2≤BMI≤32kg/m2
4. Uncontrolled blood glycemia (FPG≥7.0mmol/L and 7.5%\<HbA1c≤10%) after oral antidiabetes drugs treatment for more than 3 months
5. Treated by diet controlling, 1 secretagogue agent and another oral antidiabetes drug, with the daily dosage of the secretagogue agent not more than 50% of its maximum
6. Not participated in other clinical studies within the past 3 months
7. Well know this study and sign the informed consent form

Exclusion criteria:

1. Unable to sign the informed consent form
2. Treated by insulin, even transient usage within the past 1 year
3. Type 1 diabetes mellitus
4. Abnormal condition of gastrointestinal tract against the absorption of oral drugs
5. Insufficient of liver and kidney function: ALT≥2.5 times of the upper limit of the normal value range and serum creatinine≥the upper limit of the normal value range
6. Encountered the cardiovascular events such as the angina pectoris, myocardial infarction, severe ventricular arrhythmia, cerebral hemorrhage, cerebral infarction, heart failure ect. within the past half year
7. Usage of the other hormone medicines such as cortical hormone, immunosuppressive agents or cytotoxic drugs within the past 2 months
8. psychotic
9. Allergic history to sulfonylurea drugs
10. Diabetic coma or diabetic ketoacidosis
11. In use of the miconazole
12. Pregnancy or breeding women

Primary endpoint:

Decreasing value of FPG and HbA1c, Dosage of the insulin, Control rate of FPG

Second Endpoints:

1. MBG, SDBG, MAGE and MODD in the 48th CGMS
2. Incidence of hypoglycemia and severe hypoglycemia
3. Weight change

Eligibility criteria: Inclusion criteria:

1. Male or female with type 2 diabetes mellitus
2. 35 years old≤age≤65 years old
3. 19kg/m2≤BMI≤32kg/m2
4. Uncontrolled blood glycemia (FPG≥7.0mmol/L and 7.5%\<HbA1c≤10%) after oral antidiabetes drugs treatment for more than 3 months
5. Treated by diet controlling, 1 secretagogue agent and another oral antidiabetes drug, with the daily dosage of the secretagogue agent not more than 50% of its maximum
6. Not participated in other clinical studies within the past 3 months
7. Well know this study and sign the informed consent form

Exclusion criteria:

1. Unable to sign the informed consent form
2. Treated by insulin, even transient usage within the past 1 year
3. Type 1 diabetes mellitus
4. Abnormal condition of gastrointestinal tract against the absorption of oral drugs
5. Insufficient of liver and kidney function: ALT≥2.5 times of the upper limit of the normal value range and serum creatinine≥the upper limit of the normal value range
6. Encountered the cardiovascular events such as the angina pectoris, myocardial infarction, severe ventricular arrhythmia, cerebral hemorrhage, cerebral infarction, heart failure ect. within the past half year
7. Usage of the other hormone medicines such as cortical hormone, immunosuppressive agents or cytotoxic drugs within the past 2 months
8. psychotic
9. Allergic history to sulfonylurea drugs
10. Diabetic coma or diabetic ketoacidosis
11. In use of the miconazole
12. Pregnancy or breeding women

Primary outcomes:
measure: Decreasing value of FPG and HbA1c, dosage of insulin and control rate of FPG
timeFrame: 3 months
Secondary outcomes:
measure: MBG, SDBG, MAGE and MODD in the 48th CGMS
timeFrame: 3 months
measure: Incidence of hypoglycemia and severe hypoglycemia
timeFrame: 3 months
measure: Weight change
timeFrame: 3 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Harbin
country: China
facility: The 2nd Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College of Huazhong University of Science & Technology
state: Hubei
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: SIR RUN RUN SHAW Hospital Affiliated to Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine
name: Weiping Jia, MD, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine
name: Jian Zhou, MD, PHD
role: STUDY_DIRECTOR
affiliation: Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine
name: Yuqian Bao, MD, PHD
role: STUDY_DIRECTOR
affiliation: Guangdong Provincial People's Hospital
name: Huazhang Yang, MD, PHD
role: STUDY_DIRECTOR
affiliation: Guangdong Provincial People's Hospital
name: Jian Kuang, MD, PHD
role: STUDY_DIRECTOR
affiliation: Guangdong Provincial People's Hospital
name: Hongmei Chen, MD
role: STUDY_DIRECTOR
affiliation: West China Hospital
name: Haoming Tian, MD
role: STUDY_DIRECTOR
affiliation: SIR RUN RUN SHAW Hospital Affiliated to Zhejiang University School of Medicine
name: Hong Li, MD
role: STUDY_DIRECTOR
affiliation: SIR RUN RUN SHAW Hospital Affiliated to Zhejiang University School of Medicine
name: Fenping Zheng, MD
role: STUDY_DIRECTOR
affiliation: The Second Affiliated Hospital of Harbin Medical University
name: Qiang Li, MD
role: STUDY_DIRECTOR
affiliation: Peking University First Hospital
name: Xiaohui Guo, MD, PHD
role: STUDY_DIRECTOR
affiliation: Peking University First Hospital
name: Ying Gao, MD, PHD
role: STUDY_DIRECTOR
affiliation: Tongji Hospital
name: Muxun Zhang, MD
role: STUDY_DIRECTOR
affiliation: Beijing Hospital
name: Lixin Guo, MD, PHD
role: STUDY_DIRECTOR
affiliation: West China Hospital
name: Yan Ren, MD, PHD
role: STUDY_DIRECTOR
References:
citation: Janka HU, Plewe G, Riddle MC, Kliebe-Frisch C, Schweitzer MA, Yki-Jarvinen H. Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes. Diabetes Care. 2005 Feb;28(2):254-9. doi: 10.2337/diacare.28.2.254.
citation: Zhou J, Zheng F, Guo X, Yang H, Zhang M, Tian H, Guo L, Li Q, Mo Y, Jia W. Glargine insulin/gliclazide MR combination therapy is more effective than premixed insulin monotherapy in Chinese patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs. Diabetes Metab Res Rev. 2015 Oct;31(7):725-33. doi: 10.1002/dmrr.2661. Epub 2015 Jun 16.