In the hunt for better treatments for the growing and related epidemics of diabetes and obesity, researchers may have uncovered an unlikely drug: sugar.
Tagatose is a natural, low-calorie sugar that has been used to sweeten such things as orange juice and candy in Europe. And, for a short time, it was used in Diet Pepsi Slurpees at 7-Eleven in the United States.
But now tagatose is in a yearlong clinical trial to show that it's not just a palate pleaser but a manager for the most common form of diabetes, Type 2. If the trial goes well, it could be a big step in tagatose becoming a medicine, and eventually, an uber-sweet diet aid, according to an article in February's Diabetes, Obesity and Metabolism.
The drug-approval process is complex, costly and often fruitless. But, researchers said, small, early tests of tagatose have been promising - there were no major side effects, like with Avandia and Actos, which lower blood sugar but carry the government's strongest warning about an increased risk of heart failure.
"The idea of sugar as a treatment is provocative," said Thomas W. Donner, a University of Maryland endocrinologist and diabetes researcher who co-authored the journal article. "It's in the way it's absorbed. What we need to see is the exact amount the blood sugar is lowered."
Controlling blood sugar is crucial for all diabetics, about 7 percent of U.S. adults and children, or 20.8 million people, according to the American Diabetes Association. In nine out of 10 new cases of Type 2, the people are overweight.
With the condition, the body improperly uses or does not produce insulin, a hormone needed to convert sugar in the blood into energy in the cells. When blood sugar spikes, it can lead to complications such as cardiovascular disease, kidney problems and blindness.
Donner said a study of 30 people he ran before the current, late-stage clinical trial showed that tagatose ingested before meals blunted the rise in blood sugar, probably because tagatose is metabolized differently from table sugar, or sucrose.
Tagatose is absorbed poorly, and Donner said that might affect the way it's stored. It also might stimulate insulin secretion.
One drawback is the potential for uncomfortable digestion as the bulk of the tagatose passes through the body. On the positive side, researchers say tagatose could be the only diabetes drug raising heart-protecting good cholesterol and acting as a cell-protecting antioxidant.
Donner conducted the first clinical trials of tagatose in the 1990s with funding from the drug's developer, the Beltsville-based biotechnology firm Spherix Inc. He has no stake in Spherix and is not participating in the current trial.
Tagatose is a naturally occurring version of fructose, the sugar in fruit. Spherix derived it from whey, a dairy byproduct.
Spherix founder Gilbert V. Levin first wanted tagatose to help space explorers find life on Mars. It couldn't withstand heat, so other compounds were used in testing.
Levin then saw potential in the $2 billion artificial-sweetener market because tagatose resembled cane sugar but had 40 percent fewer calories. "Naturlose" was patented in the 1980s and won approval in the 1990s by the U.S. Food and Drug Administration for use in food.
Its big break in the United States came in 2003 with the Diet Pepsi Slurpees. A Pepsi spokeswoman said they were sold for about three years. The Danish company that Spherix licensed to make tagatose stopped production because the product didn't sell well in Europe and Australia; that made it no longer available to Pepsi.
Spherix blamed inadequate marketing. But tagatose was also expensive, making it better suited to the pharmaceutical industry that often spends hundreds of millions to develop a drug.
So Spherix dropped the sweetener business, but Levin said all the consumption proved tagatose wasn't toxic, a pitfall in many drug trials. And he'd still like to see the drug delivered in a patient-pleasing chocolate bar.
Levin said the current trial will take another year. If results are good, Levin said, he hopes to partner with a well-heeled pharmaceutical firm to take the drug to market. His small biotech firm has already sold an unrelated subsidiary and launched a consulting business to get this far.
"This could be a wonderful example of how a small company that is really determined can be successful, if we are successful," he said. "We've already gotten to a place many major companies haven't gotten."
Donner, also medical director of UM's Joslin Diabetes Center, said that if the drug works on diabetes, there could be more trials to prove it works on fat. He has already found, to his surprise, that people in past trials lost weight.
They included Cindy Nelson, a 55-year-old Baltimore resident who said her blood sugar went down significantly over a yearlong trial and she lost 18 pounds. She called that "a great bonus." She said the medication she takes daily is not controlling her sugar levels as well as tagatose did.
Her complaint with tagatose was the amount she had to consume: three or four sugar packets-worth that she put in each of four or five big cups of tea per day.
Phyllis Lee-Jordan, 65, of Baltimore said the super-sweet taste was tough. But, like Nelson, tagatose lowered her blood sugar and helped her lose a few pounds. Both said that if tagatose was easier to take - as in a chocolate bar - and proved to be safe, they would consider taking it again.
To get the same results in the meantime, Lee-Jordan said she is taking medication, watching her diet and exercising regularly.
"As you get older, you get more conscious of the illnesses that strike the body," she said. "I'm working on my weight, and I'm more conscious of what I eat. In my mind, I'm focused on not making it worse."
The rising level of obesity and disease has groups including the American Diabetes Association pushing better eating and exercise habits on the young. They are looking for more awareness, programs and laws, including one in the Maryland General Assembly to increase the frequency of gym class in some public schools.
Those efforts get a nod from doctors including Dr. Philip A. Levin, an endocrinologist and director of the Diabetes Center at Mercy who is not related to Spherix founder Levin. Philip Levin said people need to realize that they may avoid the insidious disease with diets and workouts.
And people who develop diabetes may not tolerate some drugs well. For example, the common diabetes drug Medformin has been around for decades and is effective particularly in people in early stages of diabetes, as long as they don't have kidney problems. Other drugs, such as Avandia, increase risk of heart attacks. Insulin also works, he said, except it can cause weight gain.
Doctors are always looking for better drugs, Philip Levin said. Levin has not participated in tagatose studies but said it could play an important role if it's proven effective without major side effects.
But Levin is hopeful that it can be used as a diet drug. Less obesity would mean less diabetes.
"Tagatose could be another tool for damage control," he said. "A lot of dealing with Type 2 diabetes is damage control."
What is it: Those with diabetes do not produce or properly use insulin, a hormone used to convert sugar in the bloodstream to energy in cells. It's diagnosed with a test of blood glucose levels.
Symptoms: Frequent urination, excessive thirst and hunger, unusual weight loss, fatigue, irritability and blurry vision. Over time, high levels of blood glucose may eventually cause blindness, heart disease, and nerve and kidney damage.
Cause: Unknown, though genetics, diet and exercise appear to be factors.
Who has diabetes: About 7 percent of American adults and children, or 20.8 million people. About a third are undiagnosed.
Types of diabetes: In Type 1, about 5 percent to 10 percent of cases, the body does not produce insulin. In Type 2, the bulk of the cases, the body does not use insulin properly or has an insulin deficiency. About 4 percent of cases are pregnant women affected by gestational diabetes. And another 54 million Americans are pre-diabetic (their blood glucose levels are higher than normal).
[Source: American Diabetes Association]