Efficacy and Safety Profile of Berberine Treatment in Improving Risk Factors for Cardiovascular Disease: A Systematic Review and Meta-analysis of Randomized, Double-blind Trials

Objective: This systematic review and meta-analysis aimed to evaluate the efficacy of berberine treatment in improving blood glucose, blood lipids, and blood pressure as well as the associated safety profile. Methods: PubMed, Embase, Cochrane Library, WanFang Data, and the China National Knowledge Infrastructure database were searched from the establishment of the database to December 31, 2021, to identify randomized, double-blind trials that examined the effect of berberine alone or as add-on treatment on blood glucose, blood lipids, and blood pressure with an intervention period of at least 3 months. Two researchers independently screened articles, extracted data, and assessed the quality of each study according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The efficacy outcomes included fasting blood glucose (FPG), 2-hour post-prandial glucose (2hPG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP). The safety outcome was the incidence of the total number of adverse events. Results: A total of 17 articles enrolling 1,485 participants were included in the meta-analysis. The intervention duration ranged from 12 to 24 weeks. Sixteen trials reported results for blood glucose, 14 trials reported results for blood lipids, and 7 reported results for blood pressure. Compared with placebo or baseline treatment, berberine alone or as add-on therapy significantly reduced FPG (by 0.35 mmol/L; 95% confidence interval (CI): 0.13–0.58 mmol/L; P = 0.002; I2 = 89.0%, n = 16), 2hPG (by 1.50 mmol/L; 95% CI: 0.50–2.49 mmol/L, P = 0.003, I2 = 84.1%, n = 4), HbA1c (by 0.45%, 95% CI: 0.24%–0.65%, P < 0.001, I2 = 82.8%, n = 9), TC (by 0.48 mmol/L; 95% CI: 0.36–0.60 mmol/L, P < 0.001, I2 = 72.3%, n = 13), TG (by 0.22 mmol/L; 95% CI: 0.13–0.31 mmol/L, P < 0.001, I2 = 57.1%, n = 14), and LDL-C (by 0.41 mmol/L; 95% CI: 0.34–0.48 mmol/L, P < 0.001, I2 = 35.0%, n = 12). The effect on blood glucose and blood lipids remained consistent when confined to high-quality trials. There is no significant effect of berberine treatment on HDL-C, SBP, and DBP. The incidence of the total number of adverse events was similar between the berberine group and the control group (risk ratio (RR) = 1.00, 95% CI: 0.84–1.19, P = 0.961). Gastrointestinal disorder was the most common adverse event in the berberine group and most adverse events were alleviated or disappeared as the dose was decreased or the intervention time was prolonged. Conclusions: Short-term berberine treatment significantly improved blood glucose and blood lipid profiles without raising safety concerns. A rigorously designed randomized controlled trial could be considered to examine the feasibility of the long-term application of berberine treatment in the prevention of cardiovascular disease.