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An experimental drug for DM Type-2 TTP399

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An experimental drug for Diabetes Mellitus Type-2 TTP399

Medevac of a Diabetes Mellitus patient with complications

An amazing experimental drug is on the horizon and may help people with type 2 diabetes preventing dangerous drops in blood sugar levels.

Researchers found that the compound - dubbed TTP399 for now -improved patients' blood sugar control when it was added to the regular medication metformin for six months.

Moreover, it did so without causing hypoglycemia -- blood sugar drops that, if severe, can lead to convulsions, loss of consciousness or sudden death.

The findings, published Jan. 16 in the journal Science Translational Medicine, come from an earlier "phase two" trial. Also, more research is needed before TTP399 can be added to existing armaments against type 2 diabetes, said senior researcher Carmen Valcarce.

However, she added, the effects seen so far on blood sugar control are  even better than, what's seen with current medications for the disease.

Valcarce is chief scientific officer for vTv Therapeutics, the North Carolina United States-based company developing TTP399.

Type 2 diabetes affected over 30 million Americans in 2015, according to the American Diabetes Association. It arises when the body can no longer properly use insulin, a hormone that regulates levels of glucose (sugar) in the blood. When blood sugar levels habitually soar, that can take a toll on the body over time - damaging the blood vessels and heart, nerves, kidneys and eyes. It can be life threatening too.

So while there are medications for type 2 diabetes, there's still a need for additional options of better drugs with lesser side effects, Valcarce said.

"Some people don't respond well to the current medications," she noted. "Some people can't tolerate the side effects. So this is an alternative and a better one"

Dr. Debra Simmons is an endocrinologist and professor at the University of Utah, in Salt Lake City USA.

She agreed there's a need for additional diabetes medications that work through actions that are different from available drugs. The specific underlying causes of diabetes vary from person to person, said Simmons.

TTP399 works by activating an enzyme called glucokinase, which acts as a blood sugar "sensor."

Other compounds that target glucokinase have been developed. However, they've been stymied by side effects - not only hypoglycemia but increase in triglycerides (a blood fat).

Part of the problem, according to Valcarce, is that some earlier compounds affected glucokinase in both the liver and the pancreas. Moreover, when it's activated in the pancreas, that may cause blood sugar to drop significantly.

Another issue, Simmons said, is that some compounds disturbed the way glucokinase frequently interacts with a protein that regulates it. That seemed to be spurring the rise in triglycerides.

So TTP399 was designed to avoid those serious problems.

Valcarce's team put it to the test in 190 patients with type 2 diabetes. All were already taking metformin, and some were randomly assigned to add a daily dose of TTP399. The rest of the patients added either inactive placebo pills or a diabetes drug called sitagliptin (Januvia).

After six months, patients on the new compound showed a more significant reduction in their A1c level, versus placebo patients. A1c is a measure of a person's average blood sugar level over the past three months.

There were no cases of severe blood sugar drops, the researchers said, and no adverse effects on triglycerides.

More significant, longer-term studies are still needed, Simmons said, to see how the drug's effectiveness and safety hold up.

Simmons pointed to the bigger picture: That researchers are studying the underpinnings of diabetes and trying to develop new treatment options.

However, she stressed, "diet and exercise are always going to be important in managing diabetes."

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