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

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.