Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension

Abstract

Ethnopharmacological relevance

Berberine, extracted from Coptis Root and Phellodendron Chinese, has been frequently used for the adjuvant treatment of type 2 diabetes mellitus, hyperlipidemia, and hypertension in China. Safety and efficacy studies in terms of evidence-based medical practice have become more prevalent in application to Chinese Herbal Medicine. It is necessary to assess the efficacy and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipidemia and hypertension by conducting a systematic review and meta-analysis of available clinical data.

Materials and methods

We searched the English databases PubMed, ScienceDirect, Cochrane library, EMbase, etc., and Chinese databases including China biomedical literature database (CBM), Chinese Technology Journal Full-text Database, Chinese journal full text database (CNKI), and Wanfang digital periodical full text database. Relevant studies were selected based on the inclusion and exclusion criteria. Meta-analysis was performed with RevMan5.0 software after data extraction and the quality of studies assessment.

Results

Twenty-seven randomized controlled clinical trials were included with 2569 patients. There are seven subgroups in our meta-analysis: berberine versus placebo or berberine with intensive lifestyle intervention versus intensive lifestyle intervention alone; berberine combined with oral hypoglycemic versus hypoglycemic alone; berberine versus oral hypoglycemic; berberine combined with oral lipid lowering drugs versus lipid lowering drugs alone; berberine versus oral lipid lowering drugs; berberine combined with oral hypotensor versus hypotensive medications; berberine versus oral hypotensive medications. In the treatment of type 2 diabetes mellitus, we found that berberine with lifestyle intervention tended to lower the level of FPG, PPG and HbA_1c than lifestyle intervention alone or placebo; the same as berberine combined with oral hypoglycaemics to the same hypoglycaemics; but there was no statistical significance between berberine and oral hypoglycaemics. As for the treatment of hyperlipidemia, berberine with lifestyle intervention was better than lifestyle intervention, berberine with oral lipid lowering drugs was better than lipid lowering drugs alone in reducing the level of TC and LDL-C, and raising the level of HDL-C. In the comparative study between berberine and oral lipid lowering drugs, there was no statistical significance in reducing the level of TC and LDL-C, but berberine shows better effect in lowering the level of TG and raising the level of HDL-C. In the treatment of hypertension, berberine with lifestyle intervention tended to lower the level of blood pressure more than the lifestyle intervention alone or placebo did; The same occurred when berberine combined with oral hypotensor was compared to the same hypotensor. Notably, no serious adverse reaction was reported in the 27 experiments.

Conclusion

This study indicates that berberine has comparable therapeutic effect on type 2 DM, hyperlipidemia and hypertension with no serious side effect. Considering the relatively low cost compared with other first-line medicine and treatment, berberine might be a good alternative for low socioeconomic status patients to treat type 2 DM, hyperlipidemia, hypertension over long time period. Due to overall limited quality of the included studies, the therapeutic benefit of berberine can be substantiated to a limited degree. Better methodological quality, large controlled trials using standardized preparation are expected to further quantify the therapeutic effect of berberine.

Introduction

Diabetes, hyperlipidemia and hypertension are the clinical syndromes caused by the compounding genetic and environmental factors. They are common diseases, frequently occurring on a global scale. According to the International Diabetes Federation (IDF) statistics: the number of diabetes patients worldwide in 2011 has reached 366million, an increase of nearly 30% compared with 285million in 2010 (Ge and Xu, 2013). Type 2 diabetes accounts for the type of diabetes in the vast majority of patients with diabetes (95%). One of the significant features of diabetes mellitus is a malfunctioning of lipid metabolism, which results in hyperlipidemia. Hypertension can be an independent disease or occur with diabetes and hyperlipidemia, another survey by an online medical literature analysis and retrieval system calculates the morbidity, awareness rate, treatment rate, and control rate of hypertension in different regions of world between January1980 and July 2003 (Kearney et al., 2004). The results show dissimilarity in the rate of prevalence of hypertension in different parts of the world, but overall, hypertension prevalence is increasing worldwide (Kearney et al., 2005). Currently, many new varieties of oral hypoglycemic, lipid-lowering drugs and hypotensor have been developed, and have been enlisted as treatment options, but the expensive price places a heavier burden on patients׳ financial needs. In addition, side effects occurring during the treatment might need to be reviewed to make sure the safety of berberine is evidence based.

At the beginning of the 20th century, berberine (molecular formula, C₂₀H₁₉NO₅; molecular weight, 353.36) was extracted from traditional Chinese medicine – Coptis Root (Chinese name, huáng lián) and Phellodendron Chinese (Chinese name, huáng bǎi) by Japanese and German scholars. The brand name is called Compound Berberine Tablets (fù fāng huáng lián sù piàn) (Zhang and Ji, 1999). Dozens of other plants such as Mountain Dragon (Chinese name, gǔ shān lóng), barberry root (Chinese name, sān kē zhēn), and Chinese Mahonia Stem (Chinese name, gōng láo mù) also contain berberine (Ren and Gao, 2009). The plants above are indigenous herbs that have grown in China for thousands of years. The purification of berberine has made this new tablet increasingly prevalent in clinical usage. The main component of this tablet is berberine hydrochloride, and the adjuvant materials are starch, hydroxypropyl cellulose, silica, magnesium stearate, dextrin, sucrose, and talc powder. The purity of berberine varies between plants (Lei, 2010).

Recent studies show that berberine has the clinical effect of controlling arrhythmia, lowering blood lipid, lowering blood pressure and reducing blood sugar. It also effectively promotes regeneration in Islet cells and contributes to recovery of islet function (Zhang, 2006). In terms of traditional Chinese medicine, berberine has the clinical effect of clearing “heat”, purging “fire” and removing “dampness”. As a traditional, cheap medicine, it is extensively used in the diseases of the digestive system. It is also widely used in the treatment of diabetes, hyperlipidemia and hypertension. Animal experiments have proved that berberine is able to inhibit hepatic gluconeogenesis in order to improve fasting blood sugar levels in diabetic mice without dependence on insulin levels (Xia et al., 2011). It regulates blood lipid through multiple mechanisms: increasing the expression of low density lipoprotein receptors to activate adenosine monophosphates and inhibit lipid synthesis; improving lipoprotein lipase activity; inhibiting the expression of peroxisome proliferator activated by receptor γ to retrain adipocyte differentiation; and reducing the serum free fatty acid (He et al., 2004). Moreover, according to reports in the literature, traditional Chinese medicine berberine has the effect of lowering blood pressure. Its mechanism is the enhancement of acetylcholine and peripheral vasodilatation by anti-cholinesterase (Jiangsu New Medical College, 1997).

Currently, large numbers of medical studies had been done on the treatment of berberine in diabetes, hyperlipidemia and hypertension by clinical scientists. The unique therapeutic effects and decreased side effects of berberine are well presented. But no one has done a systematic evaluation for it. This research uses the Cochrane system evaluation method and evaluates the efficacy and safety of berberine in treating type 2 diabetes, hyperlipidemia and hypertension in several randomized controlled trials. This can provide a critical reference for clinical decision making.