Quadruple Oral Combination Therapy for Type 2 Diabetes Mellitus : Glycemic Control by Thiazolidinedione (TZD) or Sodium Glucose Co-transporter 2 (SGLT-2) Inhibitor as an add-on Therapy in Type 2 Diabetes Mellitus After Failure of an Oral Triple Antidiabetic Regimen
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 121
- 试验地点
- 1
- 主要终点
- Change of HbA1c
研究概览
简要总结
In the treatment of type 2 diabetes (T2D), the number of patients requiring combination therapy of oral antidiabetic agents (OADs) is more than 70%. Especially in Korea, the tendency to avoid insulin therapy is relatively higher than other countries, therefore, the need for combination therapy of OADs is quite high. However, according to the current guidelines, clinicians are recommended to prescribe three or fewer OADs as the combination therapy for T2D. Recently, various OADs have been developed, and it is expected that quadruple combination therapy of OADs would be quite effective to lower blood glucose levels. In the present study, the investigators designed the study to compare the efficacy and safety of quadruple combination therapy; thiazolidinedione (TZD) vs. SGLT-2 inhibitor as an add-on therapy to triple combination therapy (Metformin, Sulfonylurea, Dipeptidyl peptidase-4(DPP-4) inhibitors). Quadruple combination therapy group with the SGLT-2 inhibitor will be considered as active control group, because it have shown non-inferior glycemic efficacy to the conventional insulin conversion therapy in a previous clinical study. Patients who could not achieve the target blood glucose level (7% <HbA1c ≤ 10%) under the triple combination therapy (Metformin, Sulfonylurea, DPP-4 inhibitors) for more than 12 weeks will be enrolled in this prospective, open-label, randomized, parallel comparison, multicenter clinical trial. Subjects in each group (60 patients/group) will be treated with TZD-containing quadruple therapy or SGLT-2 inhibitor-containing quadruple therapy for 24 weeks. The investigators will evaluate the glycemic efficacy and safety of each group. Primary outcome is the 24 week-change of HbA1c from baseline levels.
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
盲法说明
Open label
入排标准
- 年龄范围
- 19 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •19 ≤ age ≤ 80, male or female
- •Type 2 diabetes patients who have taken triple combination therapy of OADs as followed : Metformin (≥1000 mg/day), Sulfonylurea (Glimepiride ≥ 4 mg/day or Gliclazide ≥ 60 mg/day), DPP-4 inhibitor (Full dose) for over 12 weeks
- •At screening, 7% < HbA1c ≤ 10%
- •Patients who refused insulin therapy.
- •Subjects who understood the contents of the clinical trial and are cooperative in the trial progress, and are considered to be able to participate until the end of the trial.
- •Patients who have voluntarily agreed in writing to participate in the clinical trial after hearing the explanation of the trial.
排除标准
- •Type 1 diabetes, gestational diabetes, and other types of diabetes than type 2 diabetes mellitus.
- •Patients who have the history of allergy of hypersensitivity for the medication of the clinical trial.
- •Patients who have the history of taking TZDs or SGLT-2 inhibitors within a year prior to screening visit, or have the history of discontinuation of them due to severe side effects.
- •Patients who have the history of acute or chronic metabolic acidosis including diabetic ketoacidosis (with or without coma), or any kinds of ketosis within 12 weeks prior to screening visit.
- •Patients who have genetic metabolic diseases, such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
- •Patients who have the history of taking steroids for more than 2 weeks, within 8 weeks prior to screening visit.
- •Patients who have the history of malignancy within 5 years prior to screening visit (In case of bladder cancer, subjects will be excluded regardless of the time of diagnosis)
- •Patients who have the history of coronary artery bypass surgery or percutaneous coronary intervention, or suffered from heart failure (NYHA class III, IV)
- •Patients who have the history of uncontrolled arrhythmia, unstable angina, myocardial infarction, stroke, transient ischemic attacks, and cerebral vascular disease within 24 weeks prior to the screening date.
- •Patients of chronic renal failure, chronic kidney disease stage 3~5 (estimated glomerular filtration rate calculated vial CKD-EPI <60 mL/min/1.73m2) or on dialysis therapy.
- •Elevated liver enzymes (AST, ALT, ALP ≥ 2.5*upper limit of normal (ULN) or Total bilirubin ≥ 2.5*ULN) or Child-Pugh class B or C (for the patients of liver cirrhosis)
- •Subjects who are pregnant or lactating
- •Perioperative patients, patients with severe infections or severe trauma
- •Patients with unexamined gross hematuria
- •Any other subjects who is determined to be ineligible for the clinical trials by researchers.
研究组 & 干预措施
TZD group
Pioglitazone added to Metformin, DPP-4 inhibitors, Sulfonylurea
干预措施: TZD group (Drug)
SGLT-2 inhibitor group
Empagliflozin added to Metformin, DPP-4 inhibitors, Sulfonylurea
干预措施: SGLT-2 group (Drug)
结局指标
主要结局
Change of HbA1c
时间窗: 24 weeks
Mean difference of HbA1c after 24 week-treatment
次要结局
- glucose(24 weeks)
- Adverse events(24 weeks)
- Change of kidney function(24 weeks)
- Change of liver enzymes(24 weeks)