终点关心妍下载:Arthritis drug shows promise in Type 2 diabetes study

Arthritis drug shows promise in Type 2 diabetes study

Use of substance dates to 1500 BC

By Karen Weintraub

Globe Correspondent / March 16, 2010

A low-cost drug known since the time of the Pharaohs improved diabetes symptoms in a Boston study being published today, and its success supports an entirely new way of understanding the disease.

The drug, called salsalate, is also being studied as a potential treatment for repeat heart attacks and to stall development of Type 2 diabetes.

It’s too early to know whether the medication, commonly used to treat arthritis, can fulfill all this potential. But the new study of 108 patients, from researchers at Joslin Diabetes Center, found that patients with Type 2 diabetes were better able to process sugar when they added the medicine to their drug regimen. It was the first major study designed to evaluate the safety and effectiveness of salsalate for diabetics.

Type 2 diabetes, which affects more than 20 million Americans, generally strikes as people gain weight with age. Scientists have long struggled to understand the connection between weight gain and diabetes. The success of salsalate, which is known to have anti-inflammatory properties, suggests that the extra pounds cause chronic inflammation, triggering a cascade of problems from diabetes to heart disease to eye troubles.

“We should all exercise and reduce our body weight, but if we fail to do that, this might be a good drug,’’ said Dr. Marc Y. Donath, a diabetes researcher and professor at University Hospital in Zurich, who was not involved in the Joslin study.

Though chemically resembling aspirin, salsalate causes far fewer stomach problems and has none of the bleeding risks. It has been used for about 40 years to treat the joint pain of arthritis, with few known side effects, and sells for as little as 13 cents a pill on Drugstore.com.

The drug’s low cost might actually hurt its chances of reaching patients, though. Normally, drug companies that stand to make money off a drug pay for its research and promotion.

So far, in an unusual move, the federal government has funded the research.

Kevin J. Gorman — managing partner at Putnam Associates, a Burlington-based strategy consulting firm to the biopharmaceutical industry — said for salsalate to eventually reach patients, doctors’ organizations and insurers would have to step up and pay for marketing and perhaps some late-stage research.

Dr. Steven Shoelson, Joslin’s research director and senior author of the paper, said he is hopeful that major drug companies will get interested in the link between inflammation and diabetes, if not in this particular drug.

“If inflammation is involved, that opens up new doors for using a variety of antiinflammatory treatments,’’ said Shoelson, whose paper is appearing in the Annals of Internal Medicine.

Salsalate is a chemical copy of extracts of willow bark, which were referred to in an Egyptian medical papyrus dating to 1500 BC..

“This is one of the oldest drugs known to Western civilization,’’ Shoelson said, explaining that it was used to make poultices to draw the heat out of wounds. Its active ingredient was identified in 1876, and it began to be used to treat joint pain and diabetes. Over the next few decades, as drug companies began to promote aspirin, it replaced salsalate for pain relief. Shoelson said he assumes salsalate’s use as a diabetes drug fell off then, too.

“I think it was that people got misdirected by aspirin,’’ which he said is a better pain inhibitor than salsalate, but does nothing for diabetes.

The new research, funded by the National Institutes of Health, included 108 adults, ages 45 to 65, whose diabetes was not being well controlled by conventional medications. A quarter of the subjects received a placebo; the others were divided into three groups, each receiving a different dose of salsalate for 14 weeks, in addition to their regular diabetes medications. Dosages were reduced for patients who developed the most likely side effect, a ringing in the ears known as tinnitus, which went away at the lower doses.

Glucose levels, a measure of how well the body processes sugar, improved significantly in all three of the groups that took the medication, though several researchers not involved in the work said they had expected to see more of a change.

There was also one new potentially worrisome side effect, an increased risk of kidney problems in a few subjects, that will be explored in future research, Shoelson said.

Dr. Mitchell Lazar, director of the Institute for Diabetes, Obesity, and Metabolism at the University of Pennsylvania, said he was pleased with the results overall, but was surprised that the drug failed to lower rates of bad cholesterol and that insulin levels did not go down, other markers of effective treatments.

The connection between inflammation and diabetes suggests that the drug might also help prevent cardiovascular problems, so Joslin researchers are currently running a clinical trial on patients with heart disease (to participate, go to www.clinicaltrials.gov/ct2/show/NCT00624923), as well as a pilot study to look at whether salsalate can prevent the development of diabetes in people at risk for the disease.

A longer-term, larger study of salsalate as a diabetes treatment is also underway (to participate, go to www.clinicaltrials.gov/ct2/show/NCT00799643).

The new research comes amid other disappointments for diabetes treatments. Two studies released over the weekend found that lowering bad cholesterol and blood pressure did not reduce a diabetic patient’s risk of heart disease.

Dr. Allison Goldfine, first author on the salsalate study and head of clinical research at the Joslin, said she remains optimistic about salsalate, but will not recommend the drug to patients until more research is completed.

“I’m always very cautious when you take something from 50 people up to 3 million people,’’ she said. “This is one of the oldest drugs known to Western civilization,’’ Shoelson said, explaining that it was used to make poultices to draw the heat out of wounds. Its active ingredient was identified in 1876, and it began to be used to treat joint pain and diabetes. Over the next few decades, as drug companies began to promote aspirin, it replaced salsalate for pain relief. Shoelson said he assumes salsalate’s use as a diabetes drug fell off then, too.

“I think it was that people got misdirected by aspirin,’’ which he said is a better pain inhibitor than salsalate, but does nothing for diabetes.

The new research, funded by the National Institutes of Health, included 108 adults, ages 45 to 65, whose diabetes was not being well controlled by conventional medications. A quarter of the subjects received a placebo; the others were divided into three groups, each receiving a different dose of salsalate for 14 weeks, in addition to their regular diabetes medications. Dosages were reduced for patients who developed the most likely side effect, a ringing in the ears known as tinnitus, which went away at the lower doses.

Glucose levels, a measure of how well the body processes sugar, improved significantly in all three of the groups that took the medication, though several researchers not involved in the work said they had expected to see more of a change.

There was also one new potentially worrisome side effect, an increased risk of kidney problems in a few subjects, that will be explored in future research, Shoelson said.

Dr. Mitchell Lazar, director of the Institute for Diabetes, Obesity, and Metabolism at the University of Pennsylvania, said he was pleased with the results overall, but was surprised that the drug failed to lower rates of bad cholesterol and that insulin levels did not go down, other markers of effective treatments.

The connection between inflammation and diabetes suggests that the drug might also help prevent cardiovascular problems, so Joslin researchers are currently running a clinical trial on patients with heart disease (to participate, go to www.clinicaltrials.gov/ct2/show/NCT00624923), as well as a pilot study to look at whether salsalate can prevent the development of diabetes in people at risk for the disease.

Copyright 2010 Globe Newspaper Company.