Regimen Transition After Short-Term Intensive Insulin Therapy in Type 2 Diabetes

Официальное название

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

Обзор

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.

Вмешательства

• Препарат CSII
  Short term intensive insulin therapy
• Препарат Insulin glargine /lixisenatide Fixed Ratio Combination
  Insulin Glargine and Lixisenatide Injection(I) Treatment for 24 weeks
• Препарат Insulin Degludec and Insulin Aspart Injection
  Insulin Degludec and Insulin Aspart Injection Treatment for 24 weeks
• Препарат Insulin Glargine (HOE901 - U300)
  Insulin Glargine Treatment for 24 Weeks
• Препарат Metformin
  Metformin Treatment for 24 weeks

Первичные конечные точки

• Proportion of subjects with optimal glycemic control [Срок оценки: 24 weeks]

Вторичные конечные точки (4)

• Proportion of subjects with excellent glycemic control [Срок оценки: 24 weeks]
• Proportion of subjects with glycemic control [Срок оценки: 48 weeks]
• Medication Compliance [Срок оценки: 48 weeks]
• Incidence of adverse events [Срок оценки: 24 weeks and 48 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07173712 · IIT-2025-182

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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