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

Sun Yat-sen University

Status and phase: Completed; Phase 4

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: CSII followed by MET; Drug: CSII followed by Lina; Drug: CSII alone; Drug: CSII followed by Lina+MET

Study type: Interventional

Funder types: Other

Identifiers

NCT03194945

2016146

Details and patient eligibility

About

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.

Enrollment: 412 patients

Sex: All

Ages: 20 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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412 participants in 4 patient groups

Linagliptin plus metformin

Active Comparator group

Description:

CSII followed by Linagliptin 5 mg Qd + Metformin 0.5 g bid for 48 weeks

Treatment:

Drug: CSII followed by Lina+MET

Linagliptin

Active Comparator group

Description:

CSII followed by Linagliptin 5mg Qd for 48 weeks

Treatment:

Drug: CSII followed by Lina

Metformin

Active Comparator group

Description:

CSII followed by Metformin 0.5 bid for 48 weeks

Treatment:

Drug: CSII followed by MET

Lifestyle alone

Active Comparator group

Description:

No OHA is given after CSII

Treatment:

Drug: CSII alone