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

Kanazawa University

Status and phase: Unknown; Phase 4

Conditions: Chronic Liver Disease; Type 2 Diabetes Mellitus

Treatments: Drug: UDCA; Drug: Sitagliptin

Study type: Interventional

Funder types: Other

Identifiers

NCT01337440

KanazawaU-1

Details and patient eligibility

About

1. Objectives

2. 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.

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

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

5. Clinical hypothesis.

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

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

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

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

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

11. 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.

Enrollment: 20 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

UDCA pretreatment

Active Comparator group

Description:

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.

Treatment:

Drug: Sitagliptin

Sitagliptin pretreatment

Active Comparator group

Description:

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.

Treatment:

Drug: UDCA