Salicylate (Salsalate) in Patients With Type 2 Diabetes A Randomized Trial

Background: Short-duration studies show that salsalate improves glycemia in type 2 diabetes mellitus (T2DM). Objective: To assess 1-year efficacy and safety of salsalate in T2DM. Design: Placebo-controlled, parallel trial; computerized randomization and centralized allocation, with patients, providers, and researchers blinded to assignment. (ClinicalTrials.gov: NCT00799643) Setting: 3 private practices and 18 academic centers in the United States. Patients: Persons aged 18 to 75 years with fasting glucose levels of 12.5 mmol/L or less (<= 225 mg/dL) and hemoglobin A(1c) (HbA(1c)) levels of 7.0% to 9.5% who were treated for diabetes. Intervention: 286 participants were randomly assigned (between January 2009 and July 2011) to 48 weeks of placebo (n = 140) or salsalate, 3.5 g/d (n = 146), in addition to current therapies, and 283 participants were analyzed (placebo, n = 137; salsalate, n = 146). Measurements: Change in hemoglobin A(1c) level (primary outcome) and safety and efficacy measures. Results: The mean HbA(1c) level over 48 weeks was 0.37% lower in the salsalate group than in the placebo group (95% CI, -0.53% to -0.21%; P < 0.001). Glycemia improved despite more reductions in concomitant diabetes medications in salsalate recipients than in placebo recipients. Lower circulating leukocyte, neutrophil, and lymphocyte counts show the anti-inflammatory effects of salsalate. Adiponectin and hematocrit levels increased more and fasting glucose, uric acid, and triglyceride levels decreased with salsalate, but weight and low-density lipoprotein cholesterol levels also increased. Urinary albumin levels increased but reversed on discontinuation; estimated glomerular filtration rates were unchanged. Limitation: Trial duration and number of patients studied were insufficient to determine long-term risk-benefit of salsalate in T2DM. Conclusion: Salsalate improves glycemia in patients with T2DM and decreases inflammatory mediators. Continued evaluation of mixed cardiorenal signals is warranted.