Berberine and Metformin in the Treatment of Type 2 Diabetes Mellitus: A Systemic Review and Meta-Analysis of Randomized Clinical Trials

Objective: To assess the effects of berberine and metformin on glucose in patients with type 2 diabets mellitus (T2DM) with a systematic review and meta-analysis. Methods: The databases including PubMed, Excerpta Medica Database (EMBase), Cochrane Library, Chinese National Knowledge Infrastructure database (CNKI), WanFang, the Chinese Scientific and Technical Journals database (VIP), China Doctor Dissertation Full-text Database (CDFD) and China Master Dissertation Full-text Database (CMFD) from the inception to April 2021 in Chinese or English language were searched. Randomized controlled trials (RCTs) of berberine only or combined with metformin versus metformin were included. Data extraction and paper quality assessment were conducted according to the Cochrane Handbook. RevMan 5.4 was used for the meta-analysis. Results: A total of thirteen studies were included, covering 1173 participants. The clinical heterogeneity of the included trials was relatively high. The methodological quality of most trials was generally low with bias in terms of random sequence generation, allocation concealment, blinding method, outcome data and selective reporting. Interventions were divided into two subgroups for analysis. Meta-analysis suggested that there was no statistical significance in the hypoglycemic effect between berberine and metformin for T2DM. However, berberine combined with metformin could reduce fasting plasma glucose (FPG) [MD = −1.49, 95% CI (−2.22, −0.76), P < 0.0001], 2-hour postprandial blood glucose (2hPG) [MD = −1.89, 95% CI (−2.94, −0.84), P = 0.0004], glycosylated hemoglobin A1c (HbA1c) [MD = −0.65, 95% CI (−0.91, −0.40), P < 0.00001] and homeostasis model assessment of insulin resistance (HOMA-IR) [MD = −0.53, 95% CI (−1.03, −0.03), P = 0.04] levels significantly compared with metformin group. No severe adverse effects were reported in all trials. Conclusions: The hypoglycemic effect of berberine alone is not better than metformin. But berberine combined with metformin has good efficacy and safety in the treatment of T2DM. The current clinical studies are low in methodology and reporting quality, which needs to be further proved by more high quality, large sample size and multi-center RCTs.