Background: Chronic inflammation has been associated with the development of type 2 diabetes and cardiovascular diseases. More than 100 years ago, treatment with high dose salicylates was shown to reduce glucosuria in patients with type 2 diabetes. More recently, high dose salicylates was shown to improve several cardiometabolic risk factors. 

Objective: To determine whether treatment with salicylates at a daily dose of 1g and above compared to placebo is effective for improving cardiometabolic outcomes.

Methods: Medline, Medline in process, EMBASE, and All EBM databases were searched for studies published up to December 2015. Risk of bias and data extraction was done by two independent reviewers. Meta-analysis was conducted using random effects model.

Results: Twenty-three RCTs comprising 1301 participants were included. Salicylates were associated with decreased fasting glucose (mean difference [MD] -7.3 mg/dl, 95% CI -9.7, -4.8), glucose area under the curve (MD -7.5 mg/dl min, 95% CI -14.7, -0.3) and HbA1c (MD -0.28%, 95% CI -0.6, -0.06). In addition, salicylates were shown to increase fasting insulin (MD 2.4 µU/ml, 95% CI 0.3, 4.4), 2-hour insulin after oral glucose tolerance test (MD 25.4 µU/ml, 95% CI 8.2 to 42.6), insulin secretion (HOMA-B, MD 79.17, 95% CI 34.95, 123.39) but decreased fasting C-peptide (MD -0.11 nmol/l, 95% CI -0.2, -0.04), metabolic clearance of insulin (MD -0.26 l/min, 95% CI -0.36, -0.16) as well as triglycerides (MD -31.8 mg/dl, 95% CI -45, -18.6). Furthermore, salicylates increased plasma adiponectin levels (MD 1.9 µg/ml, 95% CI 0.9, 2.9) but did not change inflammatory markers. No significant difference was observed in insulin sensitivity measures, anthropometric measurements and blood pressure, other lipid profiles, and study withdrawal due to adverse events.

Conclusion: Salicylates appear to be safe and have beneficial effect in improving a range cardiometabolic parameters.

PROSPERO registration number: CRD42015029826