ursodeoxycholic acid + sitagliptin

This combination therapy, investigated by the Department of Endocrinology and Metabolism at Kanazawa University, involves the add-on use of ursodeoxycholic acid (UDCA) to the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin. UDCA is a naturally occurring small molecule bile acid traditionally used for liver diseases such as primary biliary cholangitis. In the context of type 2 diabetes mellitus (T2DM), UDCA is hypothesized to enhance the secretion of glucagon-like peptide-1 (GLP-1) by increasing bile acid concentrations in the small intestine and potentially activating the G protein-coupled bile acid receptor 1 (GPBAR1/TGR5). This action synergizes with sitagliptin, which prevents the degradation of GLP-1, thereby improving glycemic control and potentially increasing energy expenditure through the activation of type 2 iodothyronine deiodinase (DIO2) in brown adipose and muscle tissues. A Phase 4 clinical trial (NCT01337440) demonstrated that this combination therapy resulted in a greater reduction of HbA1c levels compared to sitagliptin monotherapy in patients with T2DM and chronic liver disease.

Other names

UDCA + sitagliptinursodiol + sitagliptinursodeoxycholic acidsitagliptin