Clinical trial NCT03194945: Effects of Sequential Treatment Based on Lina/MET After Short-term Intensive Insulin in Newly Diagnosed Type 2 Diabetes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 diabetes mellitus
Continuous subcutaneous insulin infusion
Metformin
Linagliptin
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: The Seventh Affiliated Hospital of Sun Yat-sen University
name: Guangdong Provincial Hospital of Traditional Chinese Medicine
name: Guangdong Provincial People's Hospital
name: The First Affiliated Hospital with Nanjing Medical University
name: Dongguan People's Hospital
name: Clifford Hospital
name: Guangzhou Panyu Central Hospital
name: Nanfang Hospital, Southern Medical University
name: Chinese PLA General Hospital
name: Peking University People's Hospital
name: Shanghai 10th People's Hospital
name: Shanghai Changzheng Hospital
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Huizhou Municipal Central Hospital
First posted: 2017-06-21
Enrollment: 412
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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, 412 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.


Eligibility criteria: Inclusion Criteria:

1. Patients with type 2 diabetes who have never received any hypoglycemic treatment；
2. Fasting plasma glucose (FPG) between 7.0 mmol/l (126 mg/dl) and 16.7 mmol/l (300 mg/dl);
3. glycosylated hemoglobin A1C≥8.5%;
4. Aged between 20 and 70 years 5） 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.

Primary outcomes:
measure: proportion of subjects with optimal glycemic control
timeFrame: 48 weeks
Secondary outcomes:
measure: proportion of subjects with excellent glycemic control
timeFrame: 48 weeks
measure: Change of β cell function
timeFrame: 48 weeks
measure: Change of insulin sensitivity
timeFrame: 48 weeks
measure: Incidence of adverse events
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: endocrinology department of the first affiliated hospital of Sun Yat-sen University
state: Guangdong
Study officials:
References: