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The Ancient Anti-Inflammatory Drug Salsalate Lowers Blood Glucose Levels

Value-Based Care in Cardiometabolic Health August 2012, Vol 1, No 2 - Emerging Therapies
Wayne Kuznar

The anti-inflammatory agent salsalate, used for decades as a treatment for rheumatoid arthritis, also has glucose-lowering properties, said Steven Shoelson, MD, PhD, Associate Director of Research at the Joslin Diabetes Center, Boston, and principal investigator of a placebo-controlled study of salsalate in patients with type 2 diabetes.

Salsalate lacks many of the side effects of aspirin; however, in the current study, this drug was associated with weight gain and an increase in low-density lipoprotein cholesterol (LDL-C), said Dr Shoelson.

In 2012, a 12-week study demonstrated that salsalate reduced levels of hemoglobin (Hb) A1c by approximately 0.5% at the highest dose (4 g/day).

“We now have to determine whether the degree to which this drug lowers blood glucose levels is large enough to warrant using it as an addition to the diabetes drug armamentarium,” Dr Shoelson said.

The data he presented came from a year-long trial sponsored by the National Institutes of Health. The researchers compared 3.5-g daily salsalate with placebo in 286 patients with type 2 diabetes who had a baseline HbA1c of 7.5% despite anti­diabetic treatment.

Compared with placebo, salsalate reduced HbA1c levels by 0.24% and fasting blood glucose levels by 11 mg/dL over 48 weeks. These modest improvements occurred while patients required lower doses of other diabetes medications compared with the control group.

Salsalate did reduce inflammation—white blood cell, neutrophil, and lymphocyte counts decreased from high levels to lower levels within the normal range. Although the anti- inflammatory effects of salsalate have long been known, these particular effects have not been previously documented in clinical trials. In addition, those who took salsalate saw an increase in levels of adiponectin by 21% and a decrease in uric acid levels by 11%, which suggest some cardiovascular protective qualities and a potential reduction in the risk for gout.

However, patients randomized to salsalate gained a mean of 2.2 lb more of body weight than those who received placebo, and their LDL-C levels increased by 8 mg/dL; by contrast, triglyceride levels declined.

In addition, a small change in urinary albumin of 1.8 mcg/mg of creatinine was observed in the salsalate group, which was reversed on discontinuation of the drug. This suggests that it may have an impact on kidney function; however, there was no change in glomerular filtration rate with salsalate.

There were few gastrointestinal side effects with salsalate, Dr Shoelson noted, which caused no discontinuations.

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