Treatment with high dose salicylates improves cardiometabolic parameters: Meta-analysis of randomized controlled trials.

INTRODUCTION: There is conflicting evidence regarding the efficacy of high dose salicylates in improving cardiometabolic risk in healthy and type 2 diabetes patients. We aimed to determine whether treatment with salicylates at an anti-inflammatory dose (≥1g daily) would improve cardiometabolic risk in healthy individuals and type 2 diabetes patients, compared to placebo.

METHODS: Medline, Medline-in-process, Embase, and all EBM databases were searched for studies published up to December 2016. Twenty-eight articles from 24 studies comprising 1591 participants were included. Two reviewers independently assessed the risk of bias and extracted data from included studies. Meta-analyses using random-effects model were used to analyze the data.

RESULTS: High dose salicylates (≥3g/d) decreased fasting glucose (MD -0.4mmol/l, 95% CI -0.54, -0.27) and glucose area under the curve (MD -0.41mmol/l, 95% CI -0.81, -0.01). Salicylates (≥3g/d) also increased fasting insulin (MD 2.4 μU/ml, 95% CI 0.3, 4.4), 2-h insulin (MD 25.4 μU/ml, 95% CI 8.2, 42.6), insulin secretion (MD 79.2, 95% CI 35, 123) but decreased fasting C-peptide (MD -0.11nmol/l, 95% CI -0.2, -0.04), insulin clearance (MD -0.26l/min, 95% CI -0.36, -0.16) and triglycerides (MD -0.36mmol/l, 95% CI -0.51, -0.21) and increased total adiponectin (MD 1.97μg/ml, 95% CI 0.99, 2.95). A lower salicylate dose (1-2.9g) did not change any cardiometabolic parameters (p>0.1). No significant difference was observed between those receiving salicylates and placebo following withdrawal due to adverse events.

CONCLUSIONS: High dose salicylates appear to improve cardiometabolic risk factors in healthy individuals and type 2 diabetes patients.

PROSPERO REGISTRATION NUMBER: CRD42015029826.