Efficacy and Safety of Ursodeoxycholic Acid (UDCA) Added to the DPP-4 Inhibitor in People With Type 2 Diabetes and Chronic Liver Diseases

Phase 4

• Conditions: Type 2 Diabetes Mellitus; Chronic Liver Disease
• Interventions: Drug: Sitagliptin; Drug: UDCA

• Registration Number: NCT01337440
• Lead Sponsor: Kanazawa University

Brief Summary

1. Objectives

1. 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.

2. To test whether sitagliptin enhances UDCA-induced beneficial effect in GLP-1 levels and glycemic control.

3. To test safety of combination therapy of sitagliptin and UDCA in people with type 2 diabetes.

2. Clinical hypothesis.

1. UDCA increases GLP-1 response to nutrients via provoking bile acids excretion from the liver to the intestine/colon.

2. UDCA improves glycemic control in people with type 2 diabetes.

3. Sitagliptin enhances UDCA-induced response of GLP-1 to nutrients.

4. Sitagliptin has additive beneficial effects with UDCA in glycemic control in people with type 2 diabetes.

5. Combination therapy of sitagliptin and UDCA is safe and well-tolerated in people with type 2 diabetes.

6. 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-04
• Study First Submitted: 2010-09-16
• Status Verified: 2011-04
• Study First Submitted QC: 2011-04-15
• Last Update Submitted: 2011-04-15
• Study First Posted: 2011-04-18
• Last Update Posted: 2011-04-18
• Primary Completion: 2013-03
• Study Completion: 2013-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Type 2 diabetes
2. HbA1c >=6.5% during 8 weeks prior to the study
3. Treated with none or single oral hypoglycemic agent(OHA: sulfonyl ureas, biguanides, or thiazolidinediones) over 12 weeks prior to the study

Exclusion Criteria

1. Non-Type 2 diabetes
2. Medical history and/or complication of diabetic ketoacidosis
3. Medical history and/or complication of severe hypoglycemia
4. Insulin treatment within 16 weeks prior to the study
5. Treatment with alpha-glucosidase inhibitors or sitagliptin within 12 weeks prior to the study
6. Treatment with glucocorticoid
7. Unstable glycemic control
8. Hypersensitivity to or contraindication of sitagliptin and voglibose
9. Aspartate transaminase (AST) or alanine transaminase (ALT) >=2.5 time of institutional upper normal limit
10. Uncontrolled hypertension (systolic blood pressure >160mmHg or diastolic blood pressure >100mmHg)
11. Severe health problems not suitable for the study
12. Pregnant or lactating women
13. Hepatitis B or C

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
UDCA pretreatment	Sitagliptin	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.
Sitagliptin pretreatment	UDCA	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.

Primary Outcome Measures

Name	Time	Method
the difference of haemoglobin A1c (HbA1c) and glycoalbumin (GA)	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.

Secondary Outcome Measures

Name	Time	Method
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	This is performed by power-spectrum analyses of heart rate variability

Trial Locations

Locations (1)

Internal medicine, Kanazawa university hospital; 🇯🇵 Kanazawa, Ishikawa, Japan