The Efficacy and Safety of Ursodeoxycholic Acid (UDCA) Added to the Dipeptidyl Peptidase-4 Inhibitor, Sitagliptin in People With Type 2 Diabetes and Chronic Liver Diseases
试验速览
- 阶段
- 4 期
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- the difference of haemoglobin A1c (HbA1c) and glycoalbumin (GA)
研究概览
简要总结
-
Objectives
-
To test whether Ursodeoxycholic Acid (UDCA) increases Glucagon-like peptide-1 (GLP-1) response to nutrients and improves glycemic control in people with type 2 diabetes.
-
To test whether sitagliptin enhances UDCA-induced beneficial effect in GLP-1 levels and glycemic control.
-
To test safety of combination therapy of sitagliptin and UDCA in people with type 2 diabetes.
-
Clinical hypothesis.
-
UDCA increases GLP-1 response to nutrients via provoking bile acids excretion from the liver to the intestine/colon.
-
UDCA improves glycemic control in people with type 2 diabetes.
-
Sitagliptin enhances UDCA-induced response of GLP-1 to nutrients.
-
Sitagliptin has additive beneficial effects with UDCA in glycemic control in people with type 2 diabetes.
-
Combination therapy of sitagliptin and UDCA is safe and well-tolerated in people with type 2 diabetes.
-
The combination therapy may loose weight by unique mechanisms of each agent; GLP-1 inhibits appetite by acting on CNS and gastrointestinal motility, whereas UDCA-enhanced circulating primary bile acids increases energy expenditure through the pathway involving G protein-coupled bile acid receptor 1 (Gpbar1, or M-Bar, TGR-5) and subsequent activation of type 2 iodothyronine deiodinase (D2) in brown adipose and muscle tissues, as reported previously.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 diabetes
- •HbA1c >=6.5% during 8 weeks prior to the study
- •Treated with none or single oral hypoglycemic agent(OHA: sulfonyl ureas, biguanides, or thiazolidinediones) over 12 weeks prior to the study
排除标准
- •Non-Type 2 diabetes
- •Medical history and/or complication of diabetic ketoacidosis
- •Medical history and/or complication of severe hypoglycemia
- •Insulin treatment within 16 weeks prior to the study
- •Treatment with alpha-glucosidase inhibitors or sitagliptin within 12 weeks prior to the study
- •Treatment with glucocorticoid
- •Unstable glycemic control
- •Hypersensitivity to or contraindication of sitagliptin and voglibose
- •Aspartate transaminase (AST) or alanine transaminase (ALT) >=2.5 time of institutional upper normal limit
- •Uncontrolled hypertension (systolic blood pressure >160mmHg or diastolic blood pressure >100mmHg)
- •Severe health problems not suitable for the study
- •Pregnant or lactating women
- •Hepatitis B or C
研究组 & 干预措施
UDCA pretreatment
Ursodeoxycholic Acid (UDCA) for 12 weeks, then Sitagliptin add-on therapy for additional 12 weeks.
UDCA dosage: dosing from 600 mg for initial 4 weeks. Then, if there is no adverse effect, UDCA is escalated to 900 mg, po, tid.
干预措施: Sitagliptin (Drug)
Sitagliptin pretreatment
Sitagliptin: 50 mg, po, qd for 12 weeks, then UDCA add-on therapy for additional 12 weeks.
UDCA dosage: dosing from 600 mg for initial 4 weeks. Then, if there is no adverse effect, UDCA is escalated to 900 mg, po, tid.
干预措施: UDCA (Drug)
结局指标
主要结局
the difference of haemoglobin A1c (HbA1c) and glycoalbumin (GA)
时间窗: 6 months
the difference of haemoglobin A1c (HbA1c) and glycoalbumin (GA) treating by Ursodeoxycholic Acid (UDCA)or sitagliptin monotherapy, and combination therapy of both two drugs for 3 monthes.
次要结局
- Change from Baseline in Glucagon-like peptide-1 (GLP-1) response to lipid meal test (fat 55%)(6 months)
- Change from Baseline in energy expenditure(6months)
- Change from Baseline in fasting plasma glucose level(6months)
- change from baseline in autonomic nerve function(6 months)