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
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 412
- 试验地点
- 1
- 主要终点
- proportion of subjects with optimal glycemic control
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with type 2 diabetes who have never received any hypoglycemic treatment；
- •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%;
- •Aged between 20 and 70 years 5） body mass index (BMI) 22-35 kg/m2.
排除标准
- •Type 1 diabetes or special type of diabetes;
- •Acute complications of diabetes (including DKA, HHS and lactic acidosis)
- •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;
- •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;
- •Persistently increased blood pressure >180/110 mmHg;
- •Blood creatinine clearance less than 50 ml/min, alanine aminotransferase ≥2.5×upper limit of normal, total bilirubin ≥1.5×upper limit of normal;
- •Hemoglobin <100 g/L or need regular blood transfusion;
- •Use of drugs that may influence blood glucose within 12 weeks;
- •Systemic infection or serious concomitant disease; patients with malignancy or chronic diarrhea;
- •Uncontrolled endocrine gland dysfunction;
- •Patients with mental or communication disorders;
- •Chronic cardiac insufficiency, heart function class III and above;
- •Pregnant women, lactating women and women of child bearing age who are not willing to take contraception during the study;
- •Subjects who don't cooperate, cannot be followed up or have difficulty in completing the study considered by the investigator.
研究组 & 干预措施
Linagliptin plus metformin
CSII followed by Linagliptin 5 mg Qd + Metformin 0.5 g bid for 48 weeks
干预措施: CSII followed by Lina+MET (Drug)
Linagliptin
CSII followed by Linagliptin 5mg Qd for 48 weeks
干预措施: CSII followed by Lina (Drug)
Metformin
CSII followed by Metformin 0.5 bid for 48 weeks
干预措施: CSII followed by MET (Drug)
Lifestyle alone
No OHA is given after CSII
干预措施: CSII alone (Drug)
结局指标
主要结局
proportion of subjects with optimal glycemic control
时间窗: 48 weeks
proportion of patients achieving glycosylated hemoglobin A1C \<7% at the end of sequential treatment in each treatment group.
次要结局
- Incidence of adverse events(48 weeks)
- Change of β cell function(48 weeks)
- proportion of subjects with excellent glycemic control(48 weeks)
- Change of insulin sensitivity(48 weeks)
研究者
Yanbing Li
Director of Endocrinology and Metabolism Department
First Affiliated Hospital, Sun Yat-Sen University