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

Phase 4

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: CSII followed by Lina+MET; Drug: CSII followed by Lina; Drug: CSII followed by MET; Drug: CSII alone

• Registration Number: NCT03194945
• Lead Sponsor: Sun Yat-sen University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-06-19
• Study First Submitted QC: 2017-06-19
• Study First Posted: 2017-06-21
• Study Start: 2017-11-01
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-16
• Last Update Posted: 2024-06-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 412

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Linagliptin plus metformin	CSII followed by Lina+MET	CSII followed by Linagliptin 5 mg Qd + Metformin 0.5 g bid for 48 weeks
Linagliptin	CSII followed by Lina	CSII followed by Linagliptin 5mg Qd for 48 weeks
Metformin	CSII followed by MET	CSII followed by Metformin 0.5 bid for 48 weeks
Lifestyle alone	CSII alone	No OHA is given after CSII

Primary Outcome Measures

Name	Time	Method
proportion of subjects with optimal glycemic control	48 weeks	proportion of patients achieving glycosylated hemoglobin A1C \<7% at the end of sequential treatment in each treatment group.

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse events	48 weeks	Differences in incidence of adverse events among treatment arms at the end of study.
proportion of subjects with excellent glycemic control	48 weeks	proportion of patients achieving glycosylated hemoglobin A1C \<6.5% at the end of sequential treatment in each treatment group.
Change of β cell function	48 weeks	Differences in β-cell indicators among treatment arms at the end of study.
Change of insulin sensitivity	48 weeks	Differences in insulin sensitivity indicators among treatment arms at the end of study.

Trial Locations

Locations (1)

endocrinology department of the first affiliated hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China