Effects of Sequential Treatment Based on Lina/MET After Short-term Intensive Insulin in Newly Diagnosed Type 2 Diabetes

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Effects of Linagliptin and Metformin Monotherapy or Combined Sequential Treatment After Early Short-term Intensive Insulin Treatment on Long-term Blood Glucose Control and Function of β Cells in Patients With Type 2 Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03194945
• Other study ID #: 2016146
• Status: Recruiting
• Phase: Phase 4
• Start date: November 1, 2017
• Est. completion date: December 31, 2022

Study information

• Verified date: April 2021
• Source: Sun Yat-sen University
• Contact: Liehua Liu, PHD
• Phone: +8613751748843
• Email: turkey310[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Short-term intensive insulin therapy(SIIT) is able to reverse β cell dysfunction and induce glycemic remission in patients with newly diagnosed type 2 diabetes. However, proportion of patients with response gradually decreases over time. There is no consensus on which treatment should be given in order to maintain the benefit in glycemic control and β cell recovery. In this multi-center, randomized, controlled study, effects of various sequential treatments ( metformin, linagliptin and combined with both drugs) on long-term blood glucose control as well as preservation of β cell function after SIIT were investigated. In total, 448 patients with newly diagnosed type 2 diabetes who meet the inclusive criteria will be enrolled in eight centers in China. After baseline assessments, all patients will be treated with insulin pump to achieve and maintain euglycemia for 2 weeks. After completion of intensive treatment, insulin pump will be stopped. Different treatments will be applied to patients for 48 weeks according to randomization: Group A: Linagliptin 5 mg Qd + Metformin 0.5 g bid; Group B: Linagliptin 5 mg Qd; Group C: Metformin 0.5 g bid; Group D: No oral drugs. Primary endpoint is proportion of patients achieving glycosylated hemoglobin A1C <7% at the end of the study. Secondary endpoints include proportion of patients achieving glycosylated hemoglobin A1C <6.5% at the end of study; differences in β-cell function , insulin sensitivity, GLP-1 and glucagon secretion among treatment groups, and differences in adverse events among treatment groups.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 448
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Patients with type 2 diabetes who have never received any hypoglycemic treatment, or patients with type 2 diabetes <1 year from diagnosis who have used no more than 1 type of hypoglycemic drug for no more than 1 week and discontinued for more than 4 weeks before enrollment;

2. Fasting plasma glucose (FPG) between 7.0 mmol/l (126 mg/dl) and 16.7 mmol/l (300 mg/dl); glycosylated hemoglobin A1C>8.5%;

3. Aged between 25 and 65 years, body mass index (BMI) 22-35 kg/m2.

Exclusion Criteria:

1. Type 1 diabetes or special type of diabetes;

2. Acute complications of diabetes (including DKA, HHS and lactic acidosis)

3. Serious microvascular complications: proliferative stage of retinopathy; urine AER >300 mg/g or urine protein positive, quantification >0.5 g/d; uncontrolled painful diabetic neuropathy and significant diabetic autonomic neuropathy;

4. Severe macrovascular complications: acute cerebrovascular accident, acute coronary syndrome, vascular intervention for peripheral arterial disease or amputation requiring hospitalization within 12 months prior to enrollment;

5. Persistently increased blood pressure >180/110 mmHg;

6. Blood creatinine clearance less than 50 ml/min, alanine aminotransferase =2.5×upper limit of normal, total bilirubin =1.5×upper limit of normal;

7. Hemoglobin <100 g/L or need regular blood transfusion;

8. Use of drugs that may influence blood glucose within 12 weeks;

9. Systemic infection or serious concomitant disease; patients with malignancy or chronic diarrhea;

10. Uncontrolled endocrine gland dysfunction;

11. Patients with mental or communication disorders;

12. Chronic cardiac insufficiency, heart function class III and above;

13. Pregnant women, lactating women and women of child bearing age who are not willing to take contraception during the study;

14. Subjects who don't cooperate, cannot be followed up or have difficulty in completing the study considered by the investigator.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• CSII followed by Lina+MET
short-term intensive CSII followed by Linagliptin 5mg qd and Metformin 0.5g bid for 48 weeks
• CSII followed by Lina
short-term intensive CSII followed by Linagliptin 5mg qd for 48 weeks
• CSII followed by MET
short-term intensive CSII followed by Metformin 0.5g bid for 48 weeks
• CSII alone
No OHA is given after short-term intensive CSII

Locations

Country	Name	City	State
China	endocrinology department of the first affiliated hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (9)

Lead Sponsor	Collaborator
Sun Yat-sen University	Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangdong Provincial People's Hospital, Guangzhou First People's Hospital, Nanfang Hospital of Southern Medical University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, The Third Affiliated Hospital of Guangzhou Medical University, The Third Affiliated Hospital of Southern Medical University, Zhujiang Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	proportion of subjects with optimal glycemic control	proportion of patients achieving glycosylated hemoglobin A1C <7% at the end of sequential treatment in each treatment group.	48 weeks
Secondary	proportion of subjects with excellent glycemic control	proportion of patients achieving glycosylated hemoglobin A1C <6.5% at the end of sequential treatment in each treatment group.	48 weeks
Secondary	Change of ß cell function	Differences in ß-cell indicators among treatment arms at the end of study.	48 weeks
Secondary	Change of insulin sensitivity	Differences in insulin sensitivity indicators among treatment arms at the end of study.	48 weeks
Secondary	Incidence of adverse events	Differences in incidence of adverse events among treatment arms at the end of study.	48 weeks