Abstract

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 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 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.

Highlights

  • The incidence of type 2 diabetes mellitus (T2DM) is increasing rapidly worldwide

  • Berberine combined with metformin could reduce fasting plasma glucose (FPG) [mean differences (MD) = −1.49, 95% confidence interval (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 assess

  • Metaanalysis showed that berberine combined with metformin remarkably lowered plasma concentrations of FPG [MD = −1.49, 95% CI (−2.22, −0.76), P < 0.0001], 2hPG [MD = −1.89, 95% CI (−2.94, −0.84), P = 0.0004], 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]

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Summary

Introduction

The incidence of type 2 diabetes mellitus (T2DM) is increasing rapidly worldwide. Thirty years ago, T2DM was a fairly rare occurrence in adults and was almost undocumented in children [1]. The results of Chronic Disease and the risk factors in China in 2013 showed that the prevalence rate of diabetes in adult group was 10.4% and increased to 11.2% in 2017 [3]. A derivative of biguanide, is one of the most commonly used drugs to treat T2DM, and it has been used for nearly one century [4]. Guanidine was found to have anti-diabetic properties in animals in 1918. It was toxic in clinical trials [5]. Many additional unexpected but effective roles of metformin were found. Sole medication or combination therapy with other drugs has shown to be effective to treat different diseases

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