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Oral Hepatoselective Glucokinase Activator Promising in T2DM

FRIDAY, Jan. 18, 2019 -- Use of the oral hepatoselective glucokinase activator (GKA) TTP399 for type 2 diabetes does not cause hypoglycemia and has no detrimental effect on plasma lipids or liver enzymes, according to a study published online Jan. 16 in Science Translational Medicine.

Adrian Vella, M.D., from the Mayo Clinic in Rochester, Minnesota, and colleagues reviewed the rationale for an oral hepatoselective GKA, TTP399, and its progression from preclinical to clinical development. The authors present the results of a six-month randomized, double-blind, placebo- and active-controlled phase 2 study in patients with type 2 diabetes.

The researchers found that clinically significant and sustained reduction in glycated hemoglobin occurred in those receiving TTP399, with a placebo-subtracted least squares mean hemoglobin A1c change of −0.9 percent from baseline. TTP399 at a dose of 800 mg/day also increased high-density lipoprotein cholesterol (3.2 mg/dL), decreased fasting plasma glucagon (−20 pg/mL), and decreased weight among patients weighing ≥100 kg (−3.4 kg) compared with placebo.

"Although this trial demonstrated sustained glycemic effects, additional studies will be needed to determine whether the efficacy can be maintained in longer-term applications," the authors write. "In addition, the long-term safety profile of TTP399 will need to be determined."

Several authors disclosed financial ties to vTv Therapeutics, which manufactures TTP399 and partially funded the study.

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Posted: January 2019

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