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Smart Drugs

Are We Ready For Them?

By David Mendosa

Last Update: January 16, 2001

The first smart drug to stop your blood glucose from going too high after a meal without the risk of sending it too low is about to hit the market. It should be a big help—if we are smart enough to take advantage of its benefits.

‘We are going to have to get a new mindset…’

The drug is Starlix® (nateglinide) for the treatment of type 2 diabetes. Developed by Sandoz, Starlix has an effect directly proportional to blood glucose levels, the company says, calling it "a smart drug." Sandoz is now a part of Novartis, one of the world's five largest pharmaceutical companies.

As soon as Starlix brings glucose levels down to a normal range, insulin production stops, says William (Reddy) Biggs, an endocrinologist practicing in Amarillo, Texas. Novartis asked him to test and preview the drug.

"We've seen enough clinical series to assure us that it is never going to cause [severe] hypoglycemia," he says. "But at least from the studies that I saw the incidence of hypoglycemia is going to be much lower than that of the sulfonylurea drugs or Prandin."

Like the sulfonylureas and Prandin (repaglinide), Starlix works by stimulating insulin secretion from the beta cells of the pancreas. If a drug stimulates too much insulin, hypoglycemia results.

A low incidence of mild hypoglycemia was the drug's only side effect, the company says. In the clinical trials Starlix was well tolerated with an overall safety profile comparable to a placebo.

Unlike earlier drugs that stimulate insulin secretion, Starlix is fast acting and has a short duration of activity. People will take it immediately before each meal to reduce mealtime glucose spikes, while Prandin works best if taken half an hour before eating.

But are we smart enough to take advantage of what Starlix has to offer? First, like Prandin, it needs to be taken three times a day, assuming we don't skip a meal. Dr. Biggs points out that we tend to do better with a drug that needs to be taken only once a day.

An even bigger challenge is that very few people monitor their blood glucose an hour or two after a meal, which people using Starlix will need to do to determine how effective it is and make sure that blood glucose hasn't gone too low. "We have trained everybody to monitor their blood sugars before meals," he says. "Usually with people who have type 2 diabetes we are thrilled to get two or three readings a day, and none of them are postprandial [after meals]. We are going to have to get a whole new mindset to get people to do some testing after a meal."

If using Starlix means that people will start testing their blood glucose more after their meals, it will be a good thing, says Arturo Rolla, a Boston endocrinologist. He manages two diabetes-related mailing lists where he is an active participant. He says it appears that HbA1c levels depend more on mealtime spikes than on fasting levels.

The use of Starlix could be just the thing to reorient blood glucose testing to take account of the higher blood glucose levels we have after meals. Dr. Rolla thinks that it will mean that more endocrinologists will ask people with type 2 diabetes to test two hours after a meal, rather than testing only their fasting levels. Rolla says that has been the emphasis in his practice for the past four or five years.

Starlix isn't on the U.S. market yet. Novartis filed a New Drug Application with the Food and Drug Administration on December 21, 1999. It typically takes the FDA two years to approve an NDA, although it can range from two months to seven years. Dr. Biggs thinks that Novartis hopes to launch the drug by November 2000.

In August 1999 two companies launched the drug in Japan. Yamanouchi markets it as Starsis® and Nippon HMR as Fastic®.

The safety and efficacy of Starlix look good. More than 3,700 people with type 2 diabetes participated in the tests of using it alone or in conjunction with metformin (Glucophage) for even better glucose control.

Starlix comes from the amino acid phenylalanine and has a different chemical and pharmacological structure from the other drugs available for controlling blood glucose. While several people have speculated that it is in the same class of drugs as Prandin, the company and researchers who have studied it maintain that it is a new class entirely.

"It is basically a modified amino acid that was developed by a Japanese company that made food additives," Dr. Biggs explains. "They were testing various compounds and stumbled on this drug as a glucose lowering agent. They had a poster at a conference in Prague in 1992 or 1993. The Novartis [Sandoz] folks happened to be there and picked up the license to develop the drug."

The drug works by mimicking the way the body uses its natural insulin. It restores early insulin secretion with a rapid onset and short duration of action on the beta cells of the pancreas, breaking the cycle of mealtime hyperglycemia before it can begin.

Dr. Biggs counts himself among those who prefers drugs that target insulin resistance like Avandia (rosiglitazone maleate) and Actos (pioglitazone hydrochloride) rather than those like Starlix that stimulate the beta cells to release more insulin. But Starlix stimulates the beta cell for a much shorter period than the sulfonylureas, Dr. Rolla says. He says they should therefore cause less fatigue.

In fact, we have no evidence that even sulfonylureas cause beta cells to burn out, maintains another endocrinologist, Edward S. Horton, director of clinical research at the Joslin Diabetes Center in Boston. He was the lead investigator of one the Starlix clinical trials. "I know that it is a popular conception that people have," he says, "but it is not true."

Starlix could be an important drug, Dr. Horton says. "This promises to result in better overall diabetes control."

Better control that knows when to quit sounds like a winner, especially since no other company is marketing any diabetes drug as a smart drug. "I thought that was a very smart idea on their part to come up with that," Dr. Biggs laughs. 


This article originally appeared in Diabetes Wellness Letter, September 2000, pp. 3, 8.

Update

The Food and Drug Administration approved Starlix both for use alone and with metformin on December 22, 2000.


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