A Phase IV, Multicenter, Randomized, Active Comparator Controlled Study of the Addition of Pioglitazone Compared With Glimepiride in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Alogliptin
试验速览
- 阶段
- 4 期
- 入组人数
- 154
- 试验地点
- 1
- 主要终点
- Evidence of efficacy of glycemic control indicated by the mean changes of HbA1c (%) at week 26 from baseline
研究概览
简要总结
The purpose of this study is to compare the treatment effect at week 26 between the two groups, sulfonylurea (SU, glimepiride) administration and thiazolidinedione (TZD, Pioglitazone) administration, as the third-order drug among patients whose treatment is not sufficient after the combined administration of Metformin and Alogliptin.
详细描述
- Background Complications of diabetes could cause death from stroke and myocardial infarction, and it is the chronic disease that leads to foot amputation, blindness and renal failure. According to the data of Statistics Korea, the prevalence rate of diabetes for people over 30 years old (standardization) has gradually increased from 8.6% in 2001 to 9.7% in 2010. Although diabetes is not the direct cause of death or disability, it is becoming a significant health problem across the world as it is a major illness causing complications.
Diabetic complications are very common; the patients of end-stage renal failure with diabetes were 56.7% and patients who begin renal replacement therapy with diabetes were 70.5% in 2003. The prevalence rate of eye problems including cataract, retinopathies and glaucoma in diabetic patients is 1.9 times higher than that in non-diabetic patients. In addition, it is estimated that the incidence rate of acute stroke, which is a complication of the great vessels of diabetic patients, is also 5.2 times higher than that of the general population. As diabetes could cause various complications and be dangerous, the regulation of blood glucose level is essential in order to prevent these complications.
According to the Korea National Health & Nutrition Examination Survey in 2008~2010, the rate of patients with well-controlled glycated hemoglobin of below 6.5% among diabetic patients over 30 years old is only 25%. Thus, many studies are being conducted to lower the glycated hemoglobin by administering various line drugs, alone or in combination, because the regulation of blood glucose is difficult for many diabetic patients.
When the regulation of blood glucose ends in failure with a single dose of a drug, the combination treatment is recommended. Metformin is mainly used as the first-order treatment drug, and the second and third drugs, such as dipeptidyl peptidase-4 (DPP-4) inhibitor and sulphonylurea, are recommended to use if the first one is not sufficient.
DPP-4 inhibitor is a new line of hypoglycemic agent based on incretin. It has statistically significant results for the regulation of glycated hemoglobin compared to existing oral hypoglycemic agents.
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
- 19 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects included in the study are regular type 2 diabetes outpatients of male and female with a level of 7.5%≤HbA1c<10%, despite metformin and alogliptin treatments more than 3months, between 19 and 80 years old.
- •Patients had to have a body weight of at least 55 kg and or a body mass index of 22-35 kg/m2
排除标准
- •the use of weight-lowering drugs, any investigational blood-glucose or lipid-lowering agent (other than statins or ezetimibe) within the past 3 months
- •previous treatment with systemic corticosteroids or a change in dosage of thyroid hormones in the previous 6 weeks
- •the use of insulin within the 3 months prior to screening
- •allergy or hypersensitivity to target medication or any of its components
- •history of type 1 diabetes; acute metabolic complications of diabetes (e.g. ketoacidosis or hyperosmolar state (coma or precoma)) within the preceding 6 months
- •haematological disorders
- •history of angioedema with angiotensin converting enzyme inhibitors or angiotensin receptor blockers, or treated diabetic gastric paresis
- •renal failure, moderate or severe renal impairment (creatinine clearance<50 ㎖/min; or estimated glomerular filtration rate<50 ㎖/min/1.73㎡) before screening
- •Serious heart failure or prior history of heart failure(NYHA Class Ⅲ or Ⅳ heart failure.
- •impaired hepatic function (defined as elevated serum levels of either alanine aminotransferase, aspartate aminotransferase or alkaline phosphatase 2.5-fold the upper limit of the normal range [ULN] or elevated serum total bilirubin levels 2.5-fold ULN)
- •hereditary complications (limited to lactose containing medicines) such as galactose intolerance, deficiency of Lapp lactase, glucose-galactose malabsorption syndrome, etc
- •cardiovascular disease, myocardial infarction, or in the previous 6 months; coronary angioplasty, coronary stent placement
- •serious cerebrovascular, stroke, transient ischemic attack in the previous 6 months
- •laser treatment for proliferative diabetic retinopathy
- •history of alcohol or drug abuse in the previous 3 months
- •history of all of cancers not in remission for 5 years
- •Active bladder cancer
- •experience of a major operation
- •premenopausal women who were nursing or pregnant were also ineligible for trial participation
- •external injury, acute infections, a history/presence of any other severe disease, or severe trauma
- •fasting plasma glucose (FPG) level of >239.6mg/dL
- •systolic or diastolic blood pressure >160 mmHg or >100 mmHg, respectively
- •serum creatinine level of >1.5mg/dL for men or 1.3mg/dL for women
- •fasting cholesterol >250mg/dL
- •thyroid-stimulating hormone higher than the upper limit of normal
- •hemoglobin level is below 12 g/dL for men and below 10 g/dL for women
- •fasting triglyceride levels> 5.1 mmol/l (452 mg/dL)
研究组 & 干预措施
Pioglitazone
Pioglitazone is a Pioglitazone hydrochloride, and white circle-shaped tablet. It is administered once-daily with 15mg, with or without meals. The once-daily administration begins with 15mg, and if need increase, researchers can increase up to 30mg at week 12.
干预措施: Pioglitazone (Drug)
Glimepiride
The generic name of Glimepiride is Glimepiride, and it is a green snowman-shaped tablet. The once-daily administration begins with 2mg, and if need increase, researchers can increase up to 4mg at week 12.
干预措施: Glimepiride (Drug)
结局指标
主要结局
Evidence of efficacy of glycemic control indicated by the mean changes of HbA1c (%) at week 26 from baseline
时间窗: 26 weeks
次要结局
- Evidence of changes of insulin resistance and secretion at week 26 from baseline(26 weeks)
- Evidence of changes of Lipid profile at week 26 from baseline(26 weeks)
- Evidence of efficacy of glycemic control indicated by the mean changes of HbA1c (%) at week 12 from baseline(12 weeks)
研究者
In Ju Kim
Department of Internal Medicine
Pusan National University Hospital