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Cited by 110Berberine and alkaloids researchNatural Antidiabetic Agents StudiesMetabolism, Diabetes, and Cancer

The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Open access
Guo, Jing, Chen, Hongdong, Zhang, Xueqin, Lou, Wenjiao, Zhang, Pingna, Qiu, Yuheng, Zhang, Chao, Wang, Yaoxian +1 more·2021·Oxidative Medicine and Cellular Longevity
DOI 10.1155/2021/2074610PMC PMC8696197
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Abstract

Objective . Rhizoma Coptidis is an herb that has been frequently used in many traditional formulas for the treatment of diabetic mellitus (DM) over thousands of years. Berberine, the main active component of Rhizoma Coptidis , has been demonstrated to have the potential effect of hypoglycemia. To determine the potential advantages of berberine for diabetic care, we conducted this systematic review and meta‐analysis to examine the efficacy and safety of berberine in the treatment of patients with type 2 DM. Methods . Eight databases including PubMed, Embase, Web of Science, the Cochrane library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (SinoMed), Wanfang Database, and Chinese VIP Information was searched for randomized controlled trials (RCTs) reporting clinical data regarding the use of berberine for the treatment of DM. Publication qualities were also considered to augment the credibility of the evidence. Glycemic metabolisms were the main factors studied, including glycosylated hemoglobin (HbA1c), fasting plasm glucose (FPG), and 2‐hour postprandial blood glucose (2hPG). Insulin resistance was estimated by fasting blood insulin (FINS), homeostasis model assessment‐insulin resistance (HOMA‐IR), and body mass index (BMI). Lipid profiles were also assessed, including triglyceride (TG), total cholesterol (TC), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL), along with inflammation factors such as C‐reactive protein (CRP), interleukin‐6 (IL‐6), and tumor necrosis factor‐ α (TNF‐ α ). Serum creatinine (Scr), blood urea nitrogen (BUN), and adverse events were applied to evaluate the safety of berberine. Results . Forty‐six trials were assessed. Analysis of berberine applied alone or with standard diabetic therapies versus the control group revealed significant reductions in HbA1c (MD = −0.73; 95% CI (−0.97, −0.51)), FPG (MD = −0.86, 95% CI (−1.10, −0.62)), and 2hPG (MD = −1.26, 95% CI (−1.64, −0.89)). Improved insulin resistance was assessed by lowering FINS (MD = −2.05, 95% CI (−2.62, −1.48)), HOMA‐IR (MD = −0.71, 95% CI (−1.03, −0.39)), and BMI (MD = −1.07, 95% CI (−1.76, −0.37)). Lipid metabolisms were also ameliorated via the reduction of TG (MD = −0.5, 95% CI (−0.61, −0.39)), TC (MD = 0.64, 95% CI (−0.78, −0.49)), and LDL (MD = 0.86, 95% CI (−1.06, −0.65)) and the upregulation of HDL (MD = 0.17, 95% CI (0.09, 0.25)). Additionally, berberine improved the inflammation factor. Conclusion . There is strong evidence supporting the clinical efficacy and safety of berberine in the treatment of DM, especially as an adjunctive therapy. In the future, this may be used to guide targeted clinical use of berberine and the development of medications seeking to treat patients with T2DM and dyslipidemia.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and meta-analysis of 46 randomized controlled trials found that berberine, alone or combined with standard antidiabetic therapy, improved glycemic control, insulin resistance, lipid profiles, and inflammation markers in patients with type 2 diabetes. The authors conclude berberine is supported as an adjunctive therapy, though heterogeneity and mostly Chinese trial populations limit broader application.

Key findings

  • In 46 trials with 4,158 participants (2,063 experimental, 2,095 control), berberine significantly reduced HbA1c (MD = −0.75, 95% CI −1.00 to −0.51), FPG (MD = −0.89, 95% CI −1.13 to −0.64), and 2hPG (MD = −1.31, 95% CI −1.69 to −0.93).
  • Insulin resistance indices improved: FINS decreased by 2.05 (95% CI −2.62 to −1.48), HOMA-IR by 0.71 (95% CI −1.03 to −0.39), and BMI by 1.07 (95% CI −1.76 to −0.37).
  • Lipid profiles improved: TG MD = −0.5 (95% CI −0.61 to −0.39), TC decreased by 0.64 (95% CI −0.78 to −0.49), LDL decreased by 0.86 (95% CI −1.06 to −0.66), and HDL increased (MD = 0.17, 95% CI 0.09 to 0.25).
  • Inflammation markers decreased: CRP SMD = −2.13 (95% CI −2.98 to −1.28), IL-6 decreased by 1.83 (95% CI −3.05 to −0.61), and TNF-α SMD = −1.44 (95% CI −2.72 to −0.16). Adverse events were lower with berberine than control (RR = 0.70, 95% CI 0.57 to 0.87), with no significant BUN effect.

Methods

  • Systematic review and meta-analysis conducted per Cochrane Handbook and PRISMA, registered on PROSPERO as CRD42020155086; eight databases were searched through March/April 2021 with no language or date restrictions.
  • Included RCTs of adults aged ≥18 years with T2DM or prediabetes, sample size ≥60, intervention duration ≥4 weeks, comparing berberine or Rhizoma Coptidis with placebo, lifestyle intervention, or active antihyperglycemic treatment.
  • Data were pooled in RevMan 5.4 using random-effects models when heterogeneity was present; continuous outcomes used MD or SMD, categorical outcomes used RR, with 95% CIs; heterogeneity assessed by Chi² and I²; subgroup, sensitivity, risk-of-bias, and GRADE analyses were performed.

Limitations

  • The authors state that most trials were conducted among Chinese patients, limiting widespread application; excessive statistical heterogeneity appeared in some comparisons and the primary source could not be determined; literature quality was uneven, with many studies not reporting blinding or allocation concealment; and more long-term data are needed to assess diabetic complication risk.
  • Evident from the text: many pooled analyses had very high heterogeneity (I² often >90%, e.g., HbA1c I² = 98%, FPG I² = 97%, 2hPG I² = 96%), and there are minor numerical discrepancies between the abstract and main results (e.g., HbA1c MD −0.73 vs −0.75; TC sign inconsistency in the abstract), which may complicate interpretation.

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Integrity signals

Registry

Crossref · 10.1155/2021/2074610

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 33 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In the meta-analysis, berberine decreased 2hPG level (MD = −1.31, 95% CI (−1.69, −0.93), P < 0.05, I2 = 96%).

    “the 2hPG level (MD = −1.31, 95% CI (−1.69, −0.93), P < 0.05, I2 = 96%, 95% CI (0.96, 0.97))”
    Quote in the paperSubstantial claim
  • Findingown data

    In the meta-analysis, berberine decreased FPG level (MD = −0.89, 95% CI (−1.13, −0.64), P < 0.05, I2 = 97%).

    “the FPG level (MD = −0.89, 95% CI (−1.13, −0.64), P < 0.05, I2 = 97, 95% CI (0.96, 0.97))”
    Quote in the paperSubstantial claim
  • Findingown data

    When combined with antidiabetic agents, berberine reduced FPG level (MD = −1.06, 95% CI (−1.34, −0.79), P < 0.05).

    “the FPG level (MD = −1.06, 95% CI (−1.34, −0.79), P < 0.05)”
    Quote in the paperSubstantial claim
  • Findingown data

    The BMI level of the berberine group decreased by 1.07 (95% CI (−1.76, −0.37), P < 0.05, I2 = 91%).

    “the BMI level of the berberine group decreased by 1.07 (95% CI (−1.76, −0.37), P < 0.05, I2 = 91%, 95% CI (0.87, 0.94))”
    Quote in the paperSubstantial claim
  • Findingown data

    Forty-six clinical trials were included in the quantitative meta-analysis.

    “A total of 46 clinical trials were considered and included in the quantitative meta-analysis (Figure 1).”
    Quote in the paperSubstantial claim
  • May combine two claims. 22
  • Classified as probably not a substantial claim. 21
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    A total of 4,158 participants were enrolled, including 2,063 in the experimental group and 2,095 in the control group.

    “A total of 4,158 participants were enrolled, including 2,063 participants in the experimental group and 2,095 participants in the control group.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The intervention duration ranged from 4 weeks to 6 months.

    “The intervention duration ranged from 4 weeks to 6 months.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Eleven trials compared berberine with placebo or none, while four trials compared berberine with metformin.

    “Eleven trials compared berberine with placebo or none, while four trials compared berberine with metformin.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Excessive statistical heterogeneity appeared in some comparisons and its primary source could not be determined.

    “Second, excessive statistical heterogeneity appeared in some comparisons; however, the primary source of heterogeneity could not be determined.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Berberine at routine dosage 0.6-1.5 g does not increase risk of serious adverse events.

    “In addition, this treatment did not increase the risk of serious adverse events when the routine dosage ranged from 0.6 g to 1.5 g.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Titles and abstracts were screened independently by two investigators.

    “Titles and abstracts were screened independently by two investigators.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Two reviewers independently assessed the quality of each included article using the Cochrane risk of bias assessment tool.

    “Two reviewers independently assessed the quality of each article, using the risk of bias assessment tool in the Cochrane.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Sensitivity analysis by mutual conversion between random-effects and fixed-effect models did not change the I2 value or the meta-analysis results, suggesting the findings were stable.

    “The results showed that the I2 value did not change in the mutual conversion. The results of meta-analyses were not changed either. This suggests that our findings were stable.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The protocol for this systematic review was registered on PROSPERO as CRD42020155086.

    “The protocol has been registered on PROSPERO as CRD42020155086.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Five included studies were conducted with blinding of both participants and personnel.

    “Five studies were conducted with blinding of both participants and personnel.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Data extraction was carried out independently by two authors using standard data extraction forms.

    “Data extraction was carried out independently by two authors using standard data extraction forms that included participant details, the interventions used in both treatment and control group, and the primary and secondary outcomes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Five included studies reported information on allocation concealment procedures and the blindness of outcome assessments.

    “Five studies reported information on allocation concealment procedures and the blindness of outcome assessments.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Twenty-two of the included studies provided information on random sequence generation.

    “All the included studies were RCT designs and twenty-two of them provided information on random sequence generation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    This study was performed according to the Cochrane Handbook for Systematic Reviews of Interventions and was reported according to PRISMA.

    “This study was performed according to the Cochrane Handbook for Systematic Reviews of Interventions and was reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) [19].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Page M. J. McKenzie J. E. Bossuyt P. M. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews BMJ 2021 372 10.1136/bmj.n71 PMC8005924 33782057 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The result of kappa statistics for literature screening and selection was k = 0.785, indicating good consistency.

    “As to the literature screening and selection, the result of kappa statistics was k = 0.785, indicating a good consistency.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Alkaloids from Huanglian have been widely used for the treatment of diabetes and hyperglycemia with inconspicuous toxicities and side effects.

    “Alkaloids from Huanglian have been widely used for the treatment of diabetes and hyperglycemia with inconspicuous toxicities and side effects [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Ma H. He K. Zhu J. Li X. Ye X. The anti-hyperglycemia effects of _Rhizoma Coptidis_ alkaloids: a systematic review of modern pharmacological studies of the traditional herbal medicine Fitoterapia 2019 134 210 220 10.1016/j.fitote.2019.03.003 2-s2.0-85062336581 30836124 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Berberine, used alone or combined with antidiabetic agents, significantly improved glucose and lipid metabolisms along with inflammation markers in T2DM.

    “Our findings suggested that berberine, used along or combined with antidiabetic agents, significantly improved glucose and lipid metabolisms along with inflammation markers.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    For T2DM patients, glycemic or lipid values and their variability can significantly predict all-cause mortality and the occurrence of complications, including micro- and macrovascular complications.

    “For T2DM patients, glycemic or lipid values and their variability can significantly predict all-cause mortality and the occurrence of complications, including micro- and macrovascular complications [7, 8].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7] Wan E. Y. F. Yu E. Y. T. Chin W. Y. Greater variability in lipid measurements associated with cardiovascular disease and mortality: a 10-year diabetes cohort study Diabetes, Obesity and Metabolism. 2020 22 10 1777 1788 10.1111/dom.14093 32452623 PMC7540339 source

      Not checked in the free run.

    • cites [8] Lee S. Zhou J. Wong W. T. Glycemic and lipid variability for predicting complications and mortality in diabetes mellitus using machine learning BMC Endocrine Disorders 2021 21 1 p. 94 10.1186/s12902-021-00751-4 33947391 PMC8097996 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Chronic inflammation, hyperglycemia, and dyslipidemia are all involved in insulin resistance, pathogenesis of T2DM, and systematic diabetic complications.

    “Growing evidence has indicated that chronic inflammation, hyperglycemia, and dyslipidemia are all involved in insulin resistance, pathogenesis of T2DM, and systematic diabetic complications [9, 10].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [9] Bray J. J. H. Foster‒Davies H. Salem A. Glucagon-like peptide-1 receptor agonistsimprove biomarkers of inflammation and oxidative stress: a systematic review and meta-analysis of randomised controlled trials Diabetes, obesity & metabolism 2021 23 8 1806 1822 10.1111/dom.14399 33830637 source

      Not checked in the free run.

    • cites [10] Leite M. M. Dutra M. T. da Costa M. V. G. Comparative evaluation of inflammatory parameters and substitute insulin resistance indices in elderly women with and without type 2 diabetes mellitus Experimental Gerontology 2021 150, article 111389 10.1016/j.exger.2021.111389 33957262 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Clinically tested lipid-lowering nutraceuticals including berberine could be safely used to improve lipid levels in patients with mild-to-moderate dyslipidemia.

    “Evidence suggests that clinically tested lipid-lowering nutraceuticals including berberine could be safely used to improve lipid levels in patients with mild-to-moderate dyslipidemia [71].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [71] Fogacci F. Grassi D. Rizzo M. Cicero A. F. G. Metabolic effect of berberine–silymarin association: a meta-analysis of randomized, double-blind, placebo-controlled clinical trials Phytotherapy Research 2019 33 4 862 870 10.1002/ptr.6282 2-s2.0-85059848057 30632209 PMC6590227 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    There is strong evidence supporting the clinical efficacy and safety of berberine in the treatment of DM, especially as an adjunctive therapy.

    “There is strong evidence supporting the clinical efficacy and safety of berberine in the treatment of DM, especially as an adjunctive therapy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Berberine regulates the gut microbiota, which is closely associated with systematic inflammation that adds to the progression of T2DM.

    “Additionally, evidence has shown that berberine regulates the gut microbiota as well [14, 15], which is closely associated with systematic inflammation that adds to the progression of T2DM.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] Di S. Han L. An X. _In silico_ network pharmacology and _in vivo_ analysis of berberine-related mechanisms against type 2 diabetes mellitus and its complications Journal of Ethnopharmacology 2021 276, article 114180 10.1016/j.jep.2021.114180 33957209 source

      Not checked in the free run.

    • cites [15] Zhang Y. Gu Y. Ren H. Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study) Nature Communications 2020 11 1 p. 5015 10.1038/s41467-020-18414-8 33024120 PMC7538905 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In T2DM patients, IL-6 and TNF-α levels are strikingly increased, and this is associated with downregulation of several drug metabolizing enzymes, leading to poor drug effects.

    “In T2DM patients, IL-6 and TNF-α levels are strikingly increased. This is also associated with a downregulation of several drug metabolizing enzymes, which leads to poor drug effects [11].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Darakjian L. Deodhar M. Turgeon J. Michaud V. Chronic inflammatory status observed in patients with type 2 diabetes induces modulation of cytochrome P450 expression and activity International Journal of Molecular Sciences 2021 22 9 p. 4967 10.3390/ijms22094967 34067027 PMC8124164 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Berberine is an important lead compound with a wide spectrum of pharmacological activities, including antitumor, anti-inflammatory, hypoglycemic, hypolipidemic, and antiobesity effects.

    “Among the different alkaloids, berberine is an important lead compound with a wide spectrum of pharmacological activities, including antitumor, anti-inflammatory, hypoglycemic, hypolipidemic, and antiobesity effects [13].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Kong Y. Li L. Zhao L. G. Yu P. Li D. D. A patent review of berberine and its derivatives with various pharmacological activities (2016-2020) Expert Opinion on Therapeutic Patents 2021 1 13 10.1080/13543776.2021.1974001 34455891 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Patients with T2DM are more likely to be overweight or obese, which indicates insulin resistance and dyslipidemia along with hyperglycemia.

    “Moreover, patients with T2DM are more likely to be overweight or obese, which indicates insulin resistance and dyslipidemia along with hyperglycemia [5, 6].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [5] Daousi C. Prevalence of obesity in type 2 diabetes in secondary care: association with cardiovascular risk factors Postgraduate Medical Journal 2006 82 966 280 284 10.1136/pmj.2005.039032 2-s2.0-33645924034 16597817 PMC2579635 source

      Not checked in the free run.

    • cites [6] Tong X. Bian G. Zhen Z. TCM syndrome differentiation of 2,518 T2DM cases WORLD JOURNAL OF INTEGRATED TRADITIONAL AND WESTERN MEDICINE. 2008 3 26 28

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    As an adjunctive therapy, berberine presented better reduction of HbA1c, FPG, and 2hPG.

    “As an adjunctive therapy, berberine presented better reduction of HbA1c, FPG, and 2hPG.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Berberine improves obesity and hyperlipidemia by reducing TG, TC, and LDL and increasing HDL in several metabolic disorders.

    “Whether used alone or combined with other therapies, meta-analyses [16, 72] suggested that berberine improve obesity and hyperlipidemia by reducing TG, TC, and LDL and increasing HDL in the setting of several metabolic disorders along with improving glucose metabolism.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [16] Ye Y. Liu X. Wu N. Efficacy and safety of Berberine alone for several metabolic disorders: a systematic review and meta-analysis of randomized clinical trials Frontiers in Pharmacology 2021 12 10.3389/fphar.2021.653887 PMC8107691 33981233 source

      Not checked in the free run.

    • cites [72] Wu Y. S. Li Z. M. Chen Y. T. Berberine improves inflammatory responses of diabetes mellitus in Zucker diabetic fatty rats and insulin-resistant HepG2 cells through the PPM1B pathway Journal of Immunology Research 2020 2020 32 10.1155/2020/2141508 2141508 32908938 PMC7450322 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    GRADE criteria were applied to determine the certainty in the estimate of effect for primary outcomes.

    “Additionally, GRADE criteria (Supplementary Files 3) were applied to determine the certainty in the estimate of effect for primary outcomes.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Different dosage levels of berberine and duration of treatment may have resulted in inconsistent efficacy and different disease courses.

    “Different dosage levels of berberine and the duration of treatment may have resulted in inconsistent efficacy and different disease courses.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The current study comprehensively showed the efficacy and safety of berberine for the treatment of T2DM.

    “Compared to previous meta-analyses, the current study included 46 trials and comprehensively showed the efficacy and safety of berberine for the treatment of T2DM.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Most of the trials were conducted among Chinese patients, limiting widespread application of the data.

    “First, most of the trials were conducted among Chinese patients, which limited the widespread application of this data.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    Literature qualities were uneven, although included trials were RCTs.

    “Third, literature qualities were uneven, although the included trials were RCTs.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationnone given

    Literature qualities may have influenced the results.

    “Meanwhile, the literature qualities may have influenced the results.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Berberine acts as a SIRT1 or AMPK agonist to mimic energy restriction.

    “For patients with T2DM, the main function of berberine is as a SIRT1 or AMPK agonist to mimic energy restriction [75–77] and to target on NF-κB [78] to improve insulin resistance and inflammation as well as to alleviate the activation of ox-LDL-induced macrophages [79].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [75] Shan Y. Zhang S. Gao B. Adipose tissue SIRT1 regulates insulin sensitizing and anti-inflammatory effects of berberine Frontiers in Pharmacology 2020 11, article 591227 10.3389/fphar.2020.591227 PMC7774030 33390968 source

      Not checked in the free run.

    • cites [76] Lee Y. S. Kim W. S. Kim K. H. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states Diabetes (New York, N.Y.) 2006 55 2256 2264 10.2337/db06-0006 2-s2.0-33749336146 16873688 source

      Not checked in the free run.

    • cites [77] Reddi K. K. Li H. Li W. Tetali S. D. Berberine, a phytoalkaloid, inhibits inflammatory response induced by LPS through NF-kappabeta pathway: possible involvement of the IKKalpha MOLECULES 2021 26 16 10.3390/molecules26164733 PMC8400273 34443321 source

      Not checked in the free run.

34 of 34

  • The paper relies on this without support.

    Rhizoma Coptidis has been frequently used in many traditional formulas for the treatment of diabetic mellitus over thousands of years.

    “Rhizoma Coptidis is an herb that has been frequently used in many traditional formulas for the treatment of diabetic mellitus (DM) over thousands of years.”

  • The paper relies on this without support.

    Berberine is the main active component of Rhizoma Coptidis.

    “Berberine, the main active component of Rhizoma Coptidis, has been demonstrated to have the potential effect of hypoglycemia.”

  • The paper relies on this without support.

    In T2DM, obesity and dyslipidemia bring about low-grade inflammation and increase IL-6 and TNF-α levels.

    “In T2DM, obesity and dyslipidemia bring about low-grade inflammation and factor like IL-6 and TNF-α levels were found to be strikingly increased.”

  • The paper relies on this without support.

    Berberine has comparable effects in the treatment of T2DM with antidiabetic drugs like metformin.

    “Berberine has been demonstrated to have comparable effects in the treatment of T2DM with antidiabetic drugs like metformin that display multiple targets and pathways.”

  • The paper relies on this without support.

    Dyslipidemia and inflammation are risk factors of micro- and macrovascular lesions.

    “As we all know, dyslipidemia and inflammation are risk factors of micro- and macrovascular leisures”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Abstract and results report different pooled glucose effects

    Major

    The abstract reports HbA1c, FPG, and 2hPG mean differences of −0.73, −0.86, and −1.26, respectively. The results section reports −0.75, −0.89, and −1.31 for the same pooled outcomes; the reported confidence intervals also differ.

  • Citation [70] does not match the described clinical trial

    Minor

    The discussion attributes a case-control trial reporting a 73% HOMA-IR reduction to reference [70]. The paper's reference [70] is instead an article about nutraceuticals in dyslipidemia.

  • TC mean difference has the opposite sign from its confidence interval

    Minor

    The abstract gives a positive TC mean difference of 0.64, but its entire 95% confidence interval is negative.

  • Citation [82] is described as preclinical but is a systematic review

    Minor

    The discussion describes references [81, 82] as preclinical studies. Reference [82] is titled as a systematic review of weight loss.

  • Citation [74] does not match the described CRP meta-analysis

    Minor

    The discussion cites [74] for a meta-analysis of berberine's effect on CRP. Reference [74] is a study of adipose-tissue remodeling and thermogenesis; the CRP meta-analysis is listed as [73].

  • LDL mean difference has the opposite sign from its confidence interval

    Minor

    The abstract gives a positive LDL mean difference of 0.86, but its entire 95% confidence interval is negative.

  • BUN confidence interval conflicts with its P value and significance claim

    Minor

    The reported 95% confidence interval for the BUN effect excludes zero, whereas P = 0.16 and the text says the effect is not significant.

7 of 7

The citation lists haven’t been fetched yet

References 46 · Cited by 110

Research works printed but not linked: 37

  1. International Diabetes Federation, IDF Diabetes Atlas
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Authors
Guo, J., Chen, H., Zhang, X., Lou, W., Zhang, P., Qiu, Y., Zhang, C., Wang, Y., & Liu, W. J.
Affiliations
  • Beijing University of Chinese Medicine (CN)
  • Guangdong Medical College (CN)
Corresponding author
  • Wang, Yaoxian
  • Liu, Wei Jing
ORCID
Venue
Oxidative Medicine and Cellular Longevity
Publisher
Wiley
Published
2021-01
Volume
2021
Issue
1
Pages
2074610-2074610
ISSN
  • 1942-0994 (ISSN-L)
  • 1942-0900
DOI
10.1155/2021/2074610
PMC
PMC8696197
OpenAlex
W4200189597
Semantic Scholar
83cc31010c93fad93b5bc663894ca9e39c22416a
Cited by
110
References
46
Citations by year
2026: 29 · 2025: 36 · 2024: 11 · 2023: 20 · 2022: 14
FWCI
1.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Natural Science Foundation of China (82074361, 81804083)
Topics
  • Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
berberine, type 2 diabetes, Coptidis Rhizoma, glycemic control, HbA1c, fasting blood glucose, postprandial blood glucose, insulin resistance, HOMA-IR, lipid profile, inflammatory markers, adverse events, drug safety, traditional Chinese medicine, herbal medicine, antidiabetic efficacy, adverse drug reactions
MeSH terms
Berberine, Diabetes Mellitus, Type 2, Humans, Randomized Controlled Trials as Topic

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