Although many clinical trials regarding the antidiabetic effect of berberine have been conducted a systemic review was firstly reported by Na et al. in January 2012 [34
]. The author also published the same abstract in the supplementary issue of Diabetes [35
]. Ten RCTs involving 647 Chinese patients with T2DM were included in their review. However, no meta-analysis was performed due to significant statistical heterogeneity. Thus, the author only reported the outcomes of each trial. Compared with the previous review, we added another four studies: Liu and Hu [12
], Zhang et al. [11
], Ye [16
], and Xiang et al. [21
]. We also set three subgroups in order to minimize the heterogeneity, which resulted in combing the data successfully and performing a meta-analysis. For these reasons, our systemic review differs from the previous one.
Unlike the previous review, our review indicates that berberine with lifestyle modification was more effective in terms of lowering FBG compared with lifestyle intervention alone or plus placebo. Our review also suggests that berberine has a much better effect on reducing PPG and HbA1c levels. With regard to lowering glucose and HbA1c (shown in ), berberine appeared to improve blood glucose control in terms of normalization or an obvious reduction. The similar glycaemic control was observed when berberine was compared with the conventional antidiabetic therapy. Furthermore, berberine showed additional hypoglycaemic effect when combined with the antidiabetic agents. These outcomes suggest that berberine has a potential hypoglycaemic effect, which seems to be as effective as the conventional oral hypoglycaemics.
Our review also showed that some of the plasma lipid profiles in diabetic patients were improved by the berberine intake during a two- or three-month period. But the outcomes were various regarding the different comparisons of three subgroups. When berberine and lifestyle modification were compared with lifestyle modification alone or plus placebo, plasma levels of TG, TC, and LDL-C were decreased and HDL-C was increased, indicating an additional effect on dyslipidemia. However, compared with oral hypoglyceamics, those taking berberine just showed better results for TC, and LDL-C without any effect on HDL-C. The result of plasma TG level was controversial. Compared with oral hypoglycaemics alone, the cointervention of berberine and oral hypoglycaemics did not affect plasma levels of TG, LDL-C and HDL-C while a moderate reduction of TC level was observed. Generally, berberine appeared to have an additional cholesterol-lowering effect in treating diabetes, which was also found in the patients with hyperlipidemia [36
]. However, in different subgroup comparisons berberine, showed a different effect on TG, LDL-C, and HDL-C levels. This inconsistency may be associated with the limited number, small sample size, and heterogeneity of the included trials. It was also the reason for controversial outcomes of FINS after the intervention of berberine. Therefore the additional effect of berberine on dyslipidemia and plasma insulin level, which was rarely reported in conventional hypoglycaemics, should be more carefully assessed.
In addition, berberine evaluated in our review generally appeared to be safe. The side effects were commonly gastrointestinal discomforts including constipation, diarrhea, nausea, and abdominal distension. Constipation was one of the most common gastrointestinal complaints among diabetic patients after berberine intake. It was a predictable side effect since berberine had a long history used as a remedy for diarrhea in China. But it was tolerable and relieved after reducing the dose of berberine. No severe hypoglycemia was found in the included trials.
This systematic review also has several limitations. First, all trials included were conducted among Chinese participants in the mainland of China. There was a high risk of selection bias. We were not sure if the results were valid and applicable to other ethnic origin. Second, most of the studies were of poor quality. Only one study [9
] was double-blinded and performed adequate allocation concealment. Two studies [12
] did not use blinding but performed unclear allocation concealment. The remaining eleven studies did not use blinding and allocation concealment. Thus, potential bias in selection of patients, administration of treatment, and assessment of outcomes could lead to overestimation of the therapeutic efficacy of berberine. Third, the limited number (from 4 to 7) of the trials included in each subgroup constrained the positive evidence of berberine for diabetes. During data extraction, we also found that only two or three studies provided the available data, especially for the outcomes related to plasma lipids. Quantitative subgroup analyses should not be performed when lacking insufficient data. The latter was also the reason why we were not able to draw a solid conclusion about the efficacy of berberine on dyslipidemia. Lastly, the heterogeneity between the trials included in each subgroup was also significant. It arose though the differences in the type of control method, dose of treatment, and duration of intervention of the included studies. The variation of participant age, gender, and blood glucose level at baseline may have additionally contributed to heterogeneous results. Therefore all of the outcomes should be carefully interpreted based on substantial methodological and clinical diversity.