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 (≥ 1 g 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 (≥ 3 g/d) decreased fasting glucose (MD -0.4 mmol/l, 95% CI − 0.54, − 0.27) and glucose area under the curve (MD -0.41 mmol/l, 95% CI − 0.81, − 0.01). Salicylates (≥ 3 g/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 -0.11 nmol/l, 95% CI − 0.2, − 0.04), insulin clearance (MD -0.26 l/min, 95% CI − 0.36, − 0.16) and triglycerides (MD -0.36 mmol/l, 95% CI − 0.51, − 0.21) and increased total adiponectin (MD 1.97 μg/ml, 95% CI 0.99, 2.95). A lower salicylate dose (1–2.9 g) 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.