Salicylate (Salsalate) in Patients With Type 2 Diabetes

Abstract

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 A1c (HbA1c) 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 A1c level (primary outcome) and safety and efficacy measures. Results The mean HbA1c 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. Primary Funding Source National Institutes of Health.

Oncostatin M is a potential agent for the treatment of obesity and related metabolic disorders: a study in mice

“…From the association of chronic inflammation in the adipose tissue with the development of insulin resistance [1][2][3], it can be expected that anti-inflammatory agents, such as salicylate, would be therapeutic candidates for the treatment of insulin resistance [17][18][19]. Thus, we hypothesised that OSM may exert antiinflammatory effects on adipose tissue inflammation, possibly leading to the improvement of metabolic disorders during obesity.…”

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Macrophages, fat, and the emergence of immunometabolism

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