BOSTON — Oral salsalate taken daily can reduce systemic inflammation and improve metabolic parameters in obese, nondiabetic adults, suggesting that it “may provide a novel therapeutic route for diabetes prevention,” said Dr. Amy Fleischman at the annual meeting of the Endocrine Society.
Previous studies have shown that high-dose aspirin inhibits the inhibitory kappa B kinases/nuclear factor kappa B pathway, which is known to influence inflammation, and chronic, subacute inflammation is thought to play a role in the development of insulin resistance, type 2 diabetes, and cardiovascular disease. Salicylates have also been shown to improve glucose metabolism in patients with type 2 diabetes. Although high-dose aspirin therapy is not considered a safe option for diabetes prevention in at-risk populations because of the associated bleeding risks, salsalate, a nonacetylated dimer of salicylate, “is a much weaker inhibitor of cyclooxygenase enzymes, and as such, is clinically safer,” said Dr. Fleischman of the Joslin Diabetes Center in Boston.
Dr. Fleischman and her colleagues conducted a double-blind, placebo-controlled trial of 20 nondiabetic individuals with a mean body mass index of 38 kg/m
At 1 month, the patients taking salsalate experienced a significant 8% reduction from baseline in fasting blood glucose values. Those who received placebo had a simultaneous increase in fasting blood glucose of 4% during that time. The glycemic response to glucose load, examined by oral glucose tolerance testing, improved on salsalate treatment, and worsened on placebo during the 1-month study. The glucose area under the curve improved significantly by 14% after 1 month of treatment.
Insulin levels in both study groups were unchanged, “but fasting and OGTT [oral glucose tolerance test] C-peptide levels were lower in the salsalate-treated subjects, which is consistent with what we know about salicylate's ability to inhibit insulin clearance,” she said.
Homeostasis model assessment insulin resistance calculations showed significant improvement in insulin sensitivity in patients in the salsalate group, said Dr. Fleischman, adding that “circulating inflammatory markers responded to treatment.” Specifically, mean fasting nonesterified fatty acid decreased 44%, mean C-reactive protein decreased 37%, and concentration the atheroprotective protein adiponectin increased 56%.
Salsalate treatment was generally well tolerated. Two patients in the active treatment group and one in the control group required dose reductions from 4 g to 3–3.5 g per day. At 1 month, mean salicylate levels were 17 mg/dL in the treatment group—similar to the blood salicylate levels seen with high-dose aspirin therapy. Creatinine and aspartate transaminase did not change in either group, indicating there were no toxic effects associated with salsalate therapy.
The findings also suggest that salsalate safely and effectively interferes with that inflammatory activity and by so, doing may be decrease an individual's risk of developing type 2 diabetes and cardiovascular disease, said Dr. Fleischman.
Salsalate is Food and Drug Administration approved for relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, and other rheumatic diseases.
Dr. Fleischman disclosed no conflicts of interest related to her presentation.