1035-P: VN-B101 in Combination with Metformin/Sitagliptin or Metformin/Ertugliflozin Synergistically Improves Glycemic Control in db/db Mice

Type 2 diabetes mellitus is a common chronic and progressive disease arising from a complex pathophysiology, a single pharmacological agent can only address limited pathophysiologic targets and does not provide adequate glycemic control, leading to an increasingly interest in the development of combination therapies in order to achieve the goal. Though VN-B101, the VitNovo’s leading diabetes drug candidate, has demonstrated its dual combination treatment with metformin is safe and efficacious in patients with type 2 diabetes, VN-B101 triple combination treatment has yet to be studied that may create more treatment options for diabetes patients. The major objective of the present studies was to evaluate the efficacy of VN-B101 triple combination treatment with (1) metformin/sitagliptin (DPP-4i) or (2) metformin/ertugliflozin (SGLT2i) in db/db mice. Oral glucose tolerance test (OGTT) was performed after 4 weeks of combination treatment (VN-B101: 240mg/kg/day; metformin: 150mg/kg/day; sitagliptin: 40mg/kg/day; ertugliflozin: 10mg/kg/day). The % reduction of incremental glucose AUC during OGTT in each group was calculated to evaluate the treatment effects on glycemic control. The results show (1) VN-B101 in combination with metformin/sitagliptin synergistically improves glycemic control (VN-B101 + metformin/sitagliptin: -136.9% vs. VN-B101: -26.1% and metformin/sitagliptin: -55.6%); (2) VN-B101 in combination with metformin/ertugliflozin synergistically improves glycemic control (VN-B101 + metformin/ertugliflozin: -140.1% vs. VN-B101: -26.1% and metformin/ertugliflozin: -61.5%). These exciting results open new therapeutic possibilities in the treatment of type 2 diabetes mellitus. Clinical trial of either triple combination treatments are currently conducted in Australia. Disclosure P. Wang: None. H. Chen: None.