Regimen Transition After Short-Term Intensive Insulin Therapy in Type 2 Diabetes Mellitus Patients With Inadequate Glycemic Control on Oral Hypoglycemic Agents: A Multicenter, Open-Label, Randomized Controlled Study
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 324
- 主要终点
- Proportion of subjects with optimal glycemic control
研究概览
简要总结
Failure of oral antidiabetic drugs (OADs) is a frequent challenge in patients with type 2 diabetes mellitus (T2DM), and inadequate long-term glycemic control substantially increases the risk of diabetic complications. Short-term intensive insulin therapy (SIIT) is an established approach to mitigate glucotoxicity; however, the optimal strategy to sustain long-term glycemic benefits after SIIT in T2DM patients with OAD failure remains unclear. To address this gap, we designed a randomized controlled trial to evaluate subsequent treatment options, aiming to identify a simple and effective regimen for patients with poor glycemic control who undergo SIIT.
A total of 324 eligible patients will be enrolled. After screening, previous antidiabetic regimens will be discontinued, and patients will be randomly assigned to the SIIT- iGlarLixi group (A), the SIIT-IDegAsp group (B), or the SIIT-iGlar group (C). All patients will be hospitalized for short-term insulin pump therapy, followed by 24 weeks of treatment: group A with insulin glargine/lixisenatide, group B with insulin degludec/aspart, and group C with insulin glargine U300 plus metformin. During the extension follow-up period, patients in all groups may either continue their assigned regimen or return to their original pre-study therapy. A total of 10 clinic visits are scheduled for each patient throughout the study.
Primary endpoint is proportion of patients achieving glycosylated hemoglobin A1C <7% at 24 weeks.Secondary endpoints include proportion of patients achieving glycosylated hemoglobin A1C <6.5% at 24 weeks; differences in weight gain, hypoglycemic events among treatment groups, and differences in proportion of patients continuing the assigned regimen, glycemic control and body weight at the extension follow-up period.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with type 2 diabetes mellitus (T2DM) with a disease duration of >1 year and <15 years.
- •On a stable dose of at least one oral antidiabetic drug (OAD) for ≥3 months.
- •HbA1c at screening: >8.0% if on a single OAD; >7.5% if on more than one OAD (centralized laboratory testing, or results from medical centers participating in the National Glycohemoglobin Standardization Program).
- •Age 18-70 years.
- •Body mass index (BMI) 20-35 kg/m².
- •Able and willing to comply with study requirements, including continuous glucose monitoring, self-monitoring of blood glucose, lifestyle management, and insulin-based glycemic management.
- •Agreement to use effective contraception during the study.
- •Willingness to provide written informed consent.
排除标准
- •Diagnosis of type 1 diabetes mellitus or other specific types of diabetes.
- •Receipt within 3 months prior to screening of premixed insulin therapy and/or basal-bolus insulin therapy and/or basal insulin plus OAD therapy for ≥7 cumulative days; or receipt within 1 year prior to screening of intensive insulin therapy (insulin pump or multiple daily injections); or receipt within 3 months prior to screening of GLP-1 receptor agonists; or inability to tolerate protocol-specified doses.
- •Known hypersensitivity or intolerance to study medications.
- •Acute diabetic complications (including diabetic ketoacidosis, hyperosmolar hyperglycemic state, or lactic acidosis).
- •Severe microvascular complications: proliferative diabetic retinopathy; albumin excretion rate (AER) >300 mg/g or proteinuria >0.5 g/day; uncontrolled painful diabetic neuropathy or significant autonomic neuropathy. Severe macrovascular complications: hospitalization for acute cerebrovascular accident, acute coronary syndrome, peripheral artery disease requiring intervention or amputation within the previous 12 months; unstable angina, myocardial infarction, uncontrolled arrhythmia, or severe heart failure (New York Heart Association [NYHA] class ≥III).
- •Persistent blood pressure >180/110 mmHg, or uncontrolled above 160/110 mmHg within 1 week.
- •Estimated creatinine clearance <45 mL/min/1.73 m² (calculated by CKD-EPI formula); alanine aminotransferase ≥2.5 × upper limit of normal (ULN); or total bilirubin ≥1.5 × ULN.
- •Hemoglobin <100 g/L or requiring regular blood transfusions.
- •Use within 12 weeks prior to screening of medications affecting glycemic control for >1 cumulative week, including oral/intravenous glucocorticoids, growth hormone, estrogen/progestins, high-dose diuretics, or antipsychotics. Exceptions: low-dose diuretics used for antihypertensive purposes (HCTZ <25 mg/day, indapamide ≤1.5 mg/day) and physiological thyroid hormone replacement therapy.
- •Uncontrolled endocrine disorders.
- •History or family history of medullary thyroid carcinoma, or history of multiple endocrine neoplasia syndrome type 2 (MEN2).
- •Psychiatric illness or communication disorders.
- •Systemic infection, severe comorbid conditions, malignancy, or chronic diarrhea.
- •Pregnancy, lactation, or women of childbearing potential unwilling to use contraception during the study.
- •Uncooperative participants, inability to comply with follow-up, or judged by investigators as unlikely to complete the study.
- •Any other condition deemed unsuitable by investigators, including history of acute pancreatitis, rapidly progressing gallstones, or chronic cholecystitis.
研究组 & 干预措施
iGlarLixi group
干预措施: CSII (Drug)
iGlarLixi group
干预措施: Insulin glargine /lixisenatide Fixed Ratio Combination (Drug)
IDegAsp group
干预措施: CSII (Drug)
IDegAsp group
干预措施: Insulin Degludec and Insulin Aspart Injection (Drug)
iGlar group
干预措施: Insulin Glargine (HOE901 - U300) (Drug)
iGlar group
干预措施: Metformin (Drug)
结局指标
主要结局
Proportion of subjects with optimal glycemic control
时间窗: 24 weeks
proportion of patients achieving glycosylated hemoglobin A1C \<7% at 24 weeks in each treatment group.
次要结局
- Proportion of subjects with excellent glycemic control(24 weeks)
- Proportion of subjects with glycemic control(48 weeks)
- Medication Compliance(48 weeks)
- Incidence of adverse events(24 weeks and 48 weeks)
研究者
Yanbing Li
Clinical Professor
Sun Yat-sen University