Clinical trials on a novel new type 2 diabetes treatment lowered glucose, did not increase lipids, and was well tolerated in patients with the chronic disease.
The drug is an investigative liver-selective glucokinase activator, or GK activator, referred to as TTP399. It is a key regulator of glucose homeostasis. It is a member of the Hexokinase family and is expressed in the endocrine cells of the Langerhans islets of the liver, in the L- and K-cells of the intestines, and in the neurons of the central nervous system, in particular the hypothalamus.
GK modulates blood glucose by inducing glucose-stimulated insulin release in the pancreas and by inducing glycogen formation and glucose breakdown in the liver. GK is also assumed to be involved in the regulation of glucagon in pancreas cells and incretin hormones in intestinal endocrine cells.
TTP399 was identified by TransTech Pharma using TTP Translational Technology as a lead, novel, potent, selective and oral GK activator. The compound was put through a double-blind, six-week, multiple-dose trial studying TTP399 in 120 type 2 diabetics who were previously on stable doses of metformin. Three doses were tested – 400 mg twice a day, 800 mg once a day, and 800 mg twice a day. The three groups were also compared to a placebo group.
The mean age of study participants was 57, and their mean body mass index was 31.4 kg/m, and their mean duration of diabetes was seven years. Mean daily glucose profiles were taken in all treatment groups.
Eighty-five percent of patients in the 800-mg twice-daily group reached “well controlled” status and, overall, 40 percent of patients treated with TTP399 reached “well controlled” status. No patients in the placebo group reached well-controlled blood sugar status. The most frequent adverse events included headache, dizziness and diarrhea.
Another GK activator, MK-0941, was previously tested but was unable to sustain glycemic improvements and increased blood pressure and hypoglycemic risk.
With type 2 diabetes growing in epidemic proportions both in the United States and worldwide, drug companies are eager to find new treatments for the chronic disease. Several drugs are already on the market but many carry serious risks. For example, Actos has been linked to bladder cancer, and newer treatments Byetta and Januvia have been linked to acute pancreatitis and pancreatic cancer.