Medicament for experimental diabetes better than current medications, as suggested by the results of a trial

An experimental drug can help people with type 2 diabetes lower their blood sugar without decreasing it to dangerously low levels.

The researchers discovered that the compound, called TTP399 for now, improved patients' blood sugar control when it was added to metformin, a standard drug, for six months.

And he did it without causing hypoglycemia: drops of sugar in the blood, which, if severe, can cause seizures or loss of consciousness.

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

But, he added, the effects seen so far in controlling blood sugar are comparable to, or even better than, what is seen with current medications for the disease.

Valcarce is the scientific director of vTv Therapeutics, the North Carolina-based company that develops TTP399.

Type 2 diabetes affected more than 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 glucose (sugar) levels in the blood. When blood sugar levels are usually triggered, it can affect the body over time, damaging blood vessels and the heart, nerves, kidneys and eyes.

And although there are medications for type 2 diabetes, there is still a need for additional options, said Valcarce.

"Some people do not respond well to current medications," he noted. "Some people can not tolerate side effects."

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

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

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

Other compounds that target glucokinase have been developed. But they have been hampered by side effects, not just hypoglycemia, but also increases in triglycerides (a fat in the blood).

Part of the problem, according to Valcarce, is that some previous compounds affected glucokinase in both the liver and the pancreas. And when it's activated in the pancreas, that can cause blood sugar to plummet.

Another problem, said Simmons, is that some compounds alter the way that glucokinase normally interacts with a protein that regulates it. That seemed to be stimulating the increase in triglycerides.

So TTP399 was designed to avoid those problems.

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

After six months, patients with the new compound showed a greater reduction in their A1c level, compared to patients who received placebo. A1c is a measure of the average blood sugar level of a person in the last two or three months.

There were no cases of serious blood sugar falls, the researchers said, or negative effects on triglycerides.

Larger and longer-term studies are still needed, Simmons said, to see how the medication's effectiveness and safety are maintained.

Simmons pointed to the big picture: researchers are studying the basis of diabetes and trying to develop new treatment options.

But, he emphasized, "diet and exercise will always be important in controlling diabetes."

More information

The American Diabetes Association has more information about diabetes care.

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