Salsalate lowers blood glucose and improves glycemic control in T2D, say scientists

Joslin scientists report that salsalate, a drug used to treat arthritis, lowers blood glucose and improves glycemic control in type 2 diabetes. These findings, which were published today by the Annals of Internal Medicine, provide additional evidence that salsalate may be an effective drug to treat type 2 diabetes.

The scientists became interested in studying salsalate, an anti-inflammatory drug, after research conducted by Steven Shoelson, M.D., Ph.D., Head of the Section on Pathophysiology and Molecular Pharmacology and Professor of Medicine at Harvard Medical School, identified inflammation as a factor in the development of type 2 diabetes.

Stage 1 of TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) evaluated varying doses of salsalate in 108 participants with type 2 diabetes for 14 weeks. This study was reported in the Annals of Internal Medicine in 2010. The current findings are based on Stage 2 of TINSAL-T2D, which evaluated 286 participants with type 2 diabetes for 48 weeks. The subjects' blood glucose was inadequately controlled on current diabetes medications. Participants were randomized into salsalate and placebo groups.

After 48 weeks of treatment, the mean hemoglobin A1c level (a measurement of average blood glucose control over the past six to twelve weeks) was 37 percent lower in the salsalate group compared to the placebo group. The decrease in fasting glucose concentration was 15 mg/dl greater in the salsalate group than the placebo group. Patients in the salsalate group required fewer additional diabetes medications to control their blood sugar than patients in the placebo group.

"It's exciting that salsalate is effective in lowering blood sugar," says Allison Goldfine, M.D., lead author and Head of the Section of Clinical, Behavioral and Outcomes Research, and an Associate Professor of Medicine at Harvard Medical School. "Salsalate may have an important role in diabetes treatment and may also help us learn more about how inflammation contributes to the development of type 2 diabetes."

The salsalate group also showed improvements in markers associated with coronary risk: a 9 percent reduction in triglycerides and a 27 percent increase in adiponectin, a potentially cardioprotective protein from adipocytes. Uric acid, which is associated with cardiometabolic conditions and progression of renal disease, decreased 18 percent in the salsalate group. "The reductions in these cardiovascular risk factors paralleled improved glycemia," says Dr. Goldfine. However, the salsalate group also exhibited modest increases in LDL cholesterol and urine albumin, and had a slight increase in weight, which can indicate negative effects on heart or kidney function.

Salsalate's anti-inflammatory effects were evidenced by reductions in circulating white blood cells, neutrophils and lymphocytes, which are elevated in obesity and metabolic syndrome, but all remained within normal range.

The next step in determining whether salsalate is a safe drug for use as a diabetes medication and can receive FDA approval is to assess its effects on the progression of heart disease. Dr. Goldfine is currently leading a study, TINSAL-CVD, which is evaluating how salsalate affects coronary artery plaque volume in participants with established coronary artery disease. The results should be available in two years. "The study will help us better understand the risk/benefit ratio of using salsalate to treat diabetes," says Dr. Goldfine.