A protein, called glucokinase (or GK), acts as a key regulator of sugar levels in the body, and its expression is limited to tissues that require sugar-sensing, mainly the liver and pancreatic beta cells. If blood glucose levels are deemed too high, activation of GK in the liver increases glucose utilization which in turn lowers blood glucose.
vTv Therapeutics, has developed a GK activator (GKA) that mainly works in the liver, called TTP399. In a clinical trial in people with type 2 diabetes (T2D), published this month by Science Translational Medicine, they wanted to test if administration of TTP399 was associated with a significant and sustained reduction of HbA1c from baseline to six months of treatment. The results showed that it worked, as the levels of HbA1c in the largest dose of TTP399 were significantly reduced by 0.9 percent. What’s more, in this type 2 population, TTP399 did not cause hypoglycemia, as had been the case with previous GKA that were less liver-specific, and could act in beta cells to increase insulin release. The liver selectivity of this drug, therefore, provides additional rationale for testing the therapeutic potential of TTP399 in type 1 diabetes (T1D).
Although this trial was not funded by JDRF, JDRF has an active interest in GK activators for T1D. vTv Therapeutics and JDRF joined forces in 2017, to test TTP399 in people with T1D. After careful evaluation and establishing collaborations with expert T1D clinicians, vTv is currently carrying out a phase I/II clinical trial. This trial will recruit up to 126 participants, who will receive TTP399 or a placebo as an add-on to insulin. The goal of the trial is to test safety and efficacy in reducing HbA1c after 12 weeks of treatment. For more information on this trial, or to find out if you qualify, go to the ClinicalTrials.gov page here.
If it’s anything like the clinical trial in T2D, it will be a big thing for the T1D community!