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

Kanazawa University20 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Type 2 Diabetes Mellitus

Interventions

UDCADRUG

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.

SitagliptinDRUG

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.

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

the difference of haemoglobin A1c (HbA1c) and glycoalbumin (GA)

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.

Time frame: 6 months

Secondary Outcomes

Change from Baseline in Glucagon-like peptide-1 (GLP-1) response to lipid meal test (fat 55%)

Time frame: 6 months

Change from Baseline in energy expenditure

Time frame: 6months

Change from Baseline in fasting plasma glucose level

Time frame: 6months

change from baseline in autonomic nerve function

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

Time frame: 6 months

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts