Generic Drug for Type 2 Diabetes Passes Next Clinical Hurdle

Newswise — Clinical studies of a generic drug called salsalate, widely prescribed for arthritis, now provide early promising results that it may be useful for the treatment of patients with type 2 diabetes as well.

Salsalate is an atypical non-steroidal anti-inflammatory agent that is chemically similar to aspirin but a bit easier on the stomach. In a three-month trial of people with type 2 diabetes that was led by Joslin Diabetes Center researchers, those who took the drug showed significantly improved blood glucose levels.

Starting off, the patients all had levels of hemoglobin A1C (a standard measurement that reflects blood sugar levels over several months) in the range of 7.0 to 9.5%. A significant number of those who took salsalate saw this number drop by 0.5%, a result that is in the range of several recently released diabetes therapeutics. Other tests related to glucose levels also showed substantial improvement.

“These results are exciting,” says Allison Goldfine, M.D., Joslin’s Director of Clinical Research and an Associate Professor at Harvard Medical School. “They indicate that salsalate may provide an effective, safe and inexpensive new avenue for diabetes treatment. However, these findings are preliminary. Additional studies are ongoing. At this time we do not recommend patients use this medication for their diabetes treatment until further studies are completed.”

“There is reason to think that salsalate also could have beneficial effects on atherosclerosis,” Dr. Goldfine adds. In addition to better glucose control, patients who took salsalate saw lowered triglycerides and higher levels of adiponectin, a protein thought to aid against cardiac problems.

Overall the drug appeared to be safe and to be tolerated well by patients. The study included 108 individuals, aged from 18 to 75 years, at 17 clinical sites around the United States. Patients were randomly divided into four; three groups were each given differing amounts of salsalate in three daily doses, while the fourth received placebos. All patients continued with their current regimes for managing diabetes.

Results of the study, called TINSAL-T2D (for Targeting Inflammation using Salsalate in Type 2 Diabetes), were reported online on March 16 in the Annals of Internal Medicine, with Dr. Goldfine as first author.

Joslin Investigator Steven Shoelson, M.D., Ph.D., whose research sparked the clinical trials, notes that salsalate has a long and offbeat history as potential diabetes drug. “This research started with a finding made more than 140 years ago that seemed to have been forgotten about,” says Shoelson, who is head of Joslin’s Section on Pathophysiology and Molecular Phamacology as well as a Professor at Harvard Medical School.

Dr. Shoelson studies inflammation processes in the body, which are closely linked to insulin resistance and diabetes. Back in the 1990s, he tracked down a report by a 19th-century German doctor suggesting that a chemical with anti-inflammatory properties called sodium salicylate might aid in treating diabetes. Like aspirin, sodium salicylate in high doses irritates the stomach. But salsalate, a near relative, is not so rough. Studying the drug in animal models of diabetes, Dr. Shoelson’s lab found that it appeared to work very well.

Salsalate also is a well-accepted drug, prescribed for joint pain for decades. “Phamaceutical companies were interested in the idea of an anti-inflammatory drug for diabetes, but not in this compound, because no one can own it,” he remarks. “So we went for funding to the federal government, which has been interested in a safe, effective and inexpensive new drug for diabetes.”

With continued funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Joslin scientists and their colleagues are moving ahead with a second, larger Phase III clinical trial. Volunteers are being recruited for this stage, which will study efficacy and safety in a larger group for a longer time period. (For additional information go to the study website, www.tinsalt2d.org, or www.clinicaltrials.gov/ct2/show/NCT00799643).

Additional studies are ongoing at the Joslin to look at effects of targeting inflammation using salsalate in coronary artery disease. These investigations are funded by the National Heart, Lung and Blood Institute (NHLBI) and will advance knowledge about the role of inflammation in atherosclerosis and the safety of salsalate in patients with heart disease (for additional information go to www.clinicaltrials.gov/ct2/show/NCT00624923).

Other co-authors of the AIM paper include Vivian Fonseca, M.D., of Tulane University; Kathleen A. Jablonski, Ph.D., and Laura Pyle, M.S., of George Washington University; and Myrlene A. Staten, M.D., of the NIDDK.

Clinical site investigators:

Joshua Barzilay, Kaiser Permanente, Atlanta, GASusan Braithwaite, University of North Carolina, Chapel Hill, NCWayman Wendell Cheatham, MedStar Clinical Research Centers, Washington, D.C.Jill Crandell, Albert Einstein College of Medicine, NY, NYParesh Dandona, Kaleida Health/Diabetes Endocrine Center of Western NY, Buffalo, NYCyrus Desouza, University of Nebraska Medical Center, Omaha, NEDaniel Donovan, Columbia University, College of Physicians and Surgeons, NY, NYVivian Fonseca, Tulane University, New Orleans, LAAllison Goldfine, Joslin Diabetes Center, Boston, MAKenneth Hershon, North Shore Diabetes and Endocrine Associates, New Hyde Park, NYTheodore Mazzone, University of Illinois at Chicago, Chicago, ILJanet McGill, Washington University School of Medicine, St. Louis, MOPhillip Raskin, University of Texas Southwestern, Dallas, TSVictor Lawrence Roberts, Orlando Regional Medical Center, Orlando, FLGuillermo Umpierrez, Emory University School of Medicine, Atlanta, GAWayne Warren, Chapel Medical Group, New Haven, CTSteven Wittlin, University of Rochester Medical School, Rochester, NY

Joslin Diabetes Center is the world's preeminent diabetes research and clinical care organization. Joslin is dedicated to ensuring people with diabetes live long, healthy lives and offers real hope and progress toward diabetes prevention and a cure. Founded in 1898 by Elliott P. Joslin, M.D., Joslin is an independent nonprofit institution affiliated with Harvard Medical School. For more information about Joslin, call 1-800-JOSLIN-1 or visit www.joslin.org. The Inside Joslin news page is at www.joslin.org/news/inside_joslin.html.