Salsalate, an inexpensive anti-inflammatory drug long used to treat arthritis, may be useful in treating Type 2 diabetes and possibly in preventing the disease in people at risk for developing it, according to studies at the Joslin Diabetes Center.
“We’d been wondering if we could target the [low-level chronic] inflammatory process with anti-inflammatory drugs to treat people with diabetes,” says Allison B. Goldfine, MD, lead researcher in ongoing studies investigating the usefulness of salsalate in people with diabetes and prediabetes. (Other researchers involved in these studies include Vivian Fonseca, MD, of Tulane University Health Sciences Center in New Orleans, and Paresh Dandona, MD, of the State University of New York, Buffalo.)
The researchers at Joslin have looked at a couple of classes of anti-inflammatories to see what effect they might have on blood glucose levels and insulin resistance. First, they briefly considered glucocorticosteroids, which are used to treat a wide range of inflammatory conditions, including asthma and even bad poison ivy reactions.
“The glucocorticosteroids are very effective at reducing inflammation, but they promote insulin resistance and higher blood sugar, so it was clear that they would not be useful to treat or prevent diabetes,” says Dr. Goldfine.
The researchers then looked at nonsteroidal anti-inflammatories (NSAIDs), such as aspirin. Low doses of aspirin, around 81 milligrams (mg) daily, have been shown to inhibit blood clotting and are recommended for individuals at high risk for heart disease and atherosclerosis (the buildup of plaque on artery walls). As long as 100 years ago, studies suggested that people who took very high doses of aspirin — about ten 325-mg tablets a day — seemed to experience some improvement in diabetes control, but such a high dose of aspirin has unacceptable side effects.
“Insulin sensitivity improved, blood sugar in people who had diabetes got better, and the [spiking] of blood sugar in response to meals was improved after a high dose of aspirin,” says Dr. Goldfine. However, at high doses, aspirin, which is an acid, irritates the stomach, which not only inhibits the ability of blood platelets to clot but also puts people at risk for bleeding, especially gastrointestinal bleeding.
“We thought that maybe we could design a better aspirin. And then we realized that there were other salicylates, chemically similar to aspirin, that don’t carry the same risk of bleeding.” The drug they’re studying now, salsalate, was widely used not too long ago to treat arthritis, but it got “back-shelved” when other drugs were developed for the treatment of pain and arthritis.
The researchers’ first salsalate studies showed that blood glucose control and glucose metabolism improved in people with diabetes; salsalate also lowered inflammation markers and improved levels of cholesterol and triglycerides in the blood. The second round of studies, investigating whether the drugs could have a beneficial impact on overweight people who do not have diabetes but are at risk for developing it, found that blood glucose levels improved, as did inflammatory markers and other risk factors for disease.
Dr. Goldfine’s team is currently conducting multicenter studies across the United States to determine what dosage level is appropriate for salsalate to be used as a diabetes medicine.
“We’re looking specifically at whether it lowers blood sugar and at safety issues, liver and kidney function, and tolerability,” says Dr. Goldfine.
A new, large study, TINSAL-T2D (Targeting Inflammation Using Salsalate for Type 2 Diabetes), began in September 2008. For information on this ongoing trial, visit the Web site, www.tinsal-t2d.org, or the National Institute of Health’s clinical trials Web site, http://clinicaltrials.gov (the full link is http://clinicaltrials.gov/ct2/show/NCT00624923?term=tinsal&rank=1).