Effect of Linagliptin in Comparison With Glimepiride as Add on to Metformin on Postprandial Beta Cell Function, Postprandial Metabolism and Oxidative Stress in Patients With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Postprandial increase in intact Proinsulin levels (Peak, AUC)
研究概览
简要总结
The goal of this mechanistic study is to investigate the effect of Linagliptin in comparison to Glimepiride as add on therapy on several parameters characterizing postprandial metabolism and oxidative stress in type 2 diabetic patients on stable control with metformin.
详细描述
The goal of this mechanistic study is to investigate the effect of Linagliptin in comparison to Glimepiride as add on therapy on several parameters characterizing postprandial metabolism and oxidative stress in type 2 diabetic patients on stable control with metformin.
This mechanistic phase IV study has a prospective, comparative, open, randomized, two arm and exploratory design. Overall 40 Patients will be randomized to two treatment arms both receiving Metformin at a maximally tolerated dose. In addition to that both treatment groups will receive either an individually titrated dose of Glimepiride or 5mg once daily of Linagliptin. Subsequent to a standardized meal, several parameters reflecting beta cell function, metabolism and oxidative stress will be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diabetes mellitus type 2
- •HbA1c > 6.5% - ≤ 8.5%
- •HbA1c > 7.0% - ≤ 8.5% for those patients with a significant cardiovascular history
- •Treatment with metformin at a maximum tolerated dose
- •Age 45 - 75 years (inclusively)
- •Patient consents that his/her family physician/diabetologist will be informed of trial participation.
排除标准
- •Pretreatment with PPAR gamma agonists within the last three months
- •History of type 1 diabetes
- •Uncontrolled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >90 mmHg)
- •Acute infections
- •Medical history of hypersensitivity to the study drugs or to drugs with similar chemical structures
- •History of severe or multiple allergies
- •Treatment with any other investigational drug within 3 months before trial entry.
- •Progressive fatal disease
- •History of drug or alcohol abuse in the past 2 years
- •State after kidney transplantation
- •Serum potassium > 5.5 mmol/L
- •Pregnancy or breast feeding
- •Sexually active woman of childbearing age not practicing a highly effective method of birth control as defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs, sexual abstinence or vasectomized partner.
- •Acute myocardial infarction, open heart surgery or cerebral event (stroke/TIA) within the previous 30 days
- •Any elective surgery during study participation
- •Have had more than one unexplained episode of severe hypoglycemia (defined as requiring assistance of another person due to disabling hypoglycemia) within 6 months prior to screening visit
- •History of pancreatitis
- •History of dehydration, pre-coma diabeticum or diabetic ketoacidosis
- •Acute or scheduled investigation with iodine containing radiopaque material
- •Uncontrolled unstable angina pectoris
- •History of pericarditis, myocarditis, endocarditis
- •Recent pulmonary embolism
- •Hemodynamic relevant aortic stenosis
- •Aortic aneurysm
- •Regular use of NSAID's (no acute use of NSAID within 48 hours before V2,V4,V5)
- •Lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study
- •History of respiratory, gastrointestinal, hepatic (ALAT and/or ASAT > 3 times the normal reference range), renal (Creatinine > 1.1 mg/dl in women and > 1.5 mg/dl in men ), neurological, psychiatric and/or hematological disease as judged by the investigator
- •Lactose intolerance
- •Intake of Coumarin or coumarin derived compounds such as phenprocoumon (Marcumar) or warfarin (Coumadin, Warfant)
研究组 & 干预措施
Glimepiride-ratiopharm
Glimepiride (1-4mg) as add on therapy
干预措施: Glimepiride (Drug)
Trajenta
Linagliptin 5 mg as add on therapy
干预措施: Linagliptin (Drug)
结局指标
主要结局
Postprandial increase in intact Proinsulin levels (Peak, AUC)
时间窗: 30, 60, 90, 120, 150, 180, 210, 240, 270 300 mins post test meal procedure, 3 times within 12 weeks treatment
Postprandial Proinsulin/Insulin Ratio
时间窗: after 12 weeks treatment
Fasting intact Proinsulin levels
时间窗: after 12 weeks treatment
Fasting Proinsulin/Insulin Ratio
时间窗: after 12 weeks treatment
Fasting Blood Glucose
时间窗: after 12 weeks treatment
Postprandial Blood Glucose Excursions (Peak; AUC)
时间窗: 30, 60, 90, 120, 150, 180, 210, 240, 270 300 mins post test meal procedure, 3 times within 12 weeks treatment
Fasting Lipids
时间窗: after 12 weeks treatment
Postprandial Lipids
时间窗: after 12 weeks treatment
Fasting Erythrocyte Flexibility
时间窗: after 12 weeks treatment
Postprandial Erythrocyte Flexibility
时间窗: after 12 weeks treatment
Fasting GLP-1 levels
时间窗: after 12 weeks treatment
Postprandial GLP-1 levels
时间窗: after 12 weeks treatment
Fasting cGMP
时间窗: after 12 weeks treatment
Postprandial cGMP
时间窗: after 12 weeks treatment
Fasting Calcitonin
时间窗: after 12 weeks treatment
Fasting PAI-1 levels
时间窗: after 12 weeks treatment
Postprandial PAI-1 levels
时间窗: after 12 weeks treatment
Fasting ADMA levels
时间窗: after 12 weeks treatment
Postprandial ADMA levels
时间窗: after 12 weeks treatment
Fasting Malonyldialdehyd
时间窗: after 12 weeks treatment
fasting oxidatively modified nucleosides 8-oxodG and 8-oxoGuo
时间窗: after 12 weeks treatment
次要结局
- Hypoglycemic events(after 12 weeks treatment)
- Body Weight(after 12 weeks treatment)
研究者
Marcus Borchert
Prof. Dr. Thomas Forst
ikfe-CRO GmbH