Abstract Body

Despite more physiologic insulin analogs, continuous glucose monitoring (CGM), and continuous subcutaneous insulin infusion (CSII) therapy, a minority of patients with type 1 diabetes (T1D) achieve adequate glycemic control, and hospitalizations for diabetic ketoacidosis (DKA) and hypoglycemia are increasing globally. Several therapies for the treatment of type 2 diabetes have been evaluated as potential adjunctive treatment for T1D, however they have either had no effect in T1D or improved glycemic control, but at increased risk for life-threatening complications like DKA or hypoglycemia.

Approaches that harness the body’s existing glucose regulatory machinery may be the solution to the need for adjunctive therapies providing effective glycemic control while minimizing the frequency and severity of hypoglycemia and DKA. The novel hepato-selective glucokinase (GK) activator TTP399 was developed to preserve the physiologic relationship between GK and GK Regulatory Protein. Therefore, TTP399 only enhances GK activity during periods of hyperglycemia, thus limiting risk of hypoglycemia. The data from the SimpliciT1 study, showed the potential of TTP399 to significantly lower HbA1c, improve time in range, and reduce hypoglycemia in the absence of an increase in blood ketones. If confirmed in phase 3, adding TTP399 to insulin would represent a substantial improvement over insulin administration alone for the treatment of T1D.

While a cure for T1D remains the long-term objective, novel adjunctive therapies such as TTP399 may have an important role to play by enabling patients with T1D to achieve and maintain glycemic control without the fear and negative health effects of hypoglycemia and DKA.