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Cited by 13Berberine and alkaloids researchNatural Antidiabetic Agents StudiesDiabetes Treatment and Management

Effects of administering berberine alone or in combination on type 2 diabetes mellitus: a systematic review and meta-analysis

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Wang, Jiacheng, Bi, Chenhao, Xi, Hongbin, Wei, Fengqin·2024·Frontiers in Pharmacology
DOI 10.3389/fphar.2024.1455534PMC PMC11617981
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Abstract

Background: Despite the availability of multiple therapies for Type 2 diabetes mellitus (T2DM), challenges remain due to side effects and efficacy limitations. Berberine (BBR) has shown broad anti-diabetic effects, prompting a systematic assessment of its efficacy and safety through a meta-analysis. Methods: A comprehensive search was conducted across eight database and search engines from inception until 06/09/2024. Only randomized controlled trials (RCTs) meeting inclusion criteria were analyzed. The Cochrane risk of bias assessment tool and Jadad scale were used to evaluate study quality. Meta-analysis was performed using RevMan v5.3 and Stata/SE v15.1. Results: Fifty studies involving 4,150 participants were included. BBR alone significantly reduced fasting plasma glucose (FPG) (MD = −0.59 mmol/L, p = 0.048), 2-h postprandial blood glucose (2hPBG) (MD = −1.57 mmol/L, p < 0.01), low-density lipoprotein cholesterol (LDL-C) (MD = −0.30 mmol/L, p < 0.01), total cholesterol (TC) (MD = −0.30 mmol/L, p = 0.034), and triglycerides (TG) (MD = −0.35 mmol/L, p < 0.01). When combined with hypoglycemic drugs, BBR significantly improved FPG (MD = −0.99 mmol/L, p < 0.01), 2hPBG (MD = −1.07 mmol/L, p < 0.01), glycated hemoglobin (HbA1c) (MD = −0.69%, p < 0.01), and other metabolic markers, including fasting insulin (Fins), homeostasis model assessment index for assessing insulin resistance (HOMA-IR), lipid profiles and inflammatory markers. The most common BBR dosage was 0.9–1.5 g/d, with treatment cycles typically lasting 1–3 months. Conclusion: Current evidence suggests that BBR alone or in combination has significant potential for treating type 2 diabetes mellitus (T2DM). Future research should encompass a broader scope, including not just the beneficial effects of BBR in head-to-head studies, but more crucially, delving into its mechanisms of action with hypoglycemic drugs to optimize T2DM treatment strategies.

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  • Berberine's intrinsic hypoglycemic effect adds to that of antidiabetic agents, such as sulfonylureas and insulin, increasing the risk of hypoglycemia.

    “Its intrinsic hypoglycemic effect adds to that of antidiabetic agents, such as sulfonylureas and insulin, increasing the risk of hypoglycemia [30,38].”

    From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [30]

    The Results (section 3.4; page unavailable) find that adding berberine to sulfonylureas improved HbA1c more than sulfonylureas alone, but found no significant additional HbA1c benefit with insulin. The paper does not establish an increased risk of hypoglycemia from either combination; its Discussion instead describes a possible reduction in hypoglycemic events, and its adverse-events section reports fewer adverse reactions in some combination groups. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The first theoretical dimension of the berberine-GLP-1 combination is pharmacodynamic: berberine's hypoglycemic effect adds to that of the agonist and of any background antidiabetic agent.

    “The first is pharmacodynamic: berberine’s hypoglycemic effect adds to that of the agonist and of any background antidiabetic agent [30,38].”

    From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [30]

    The Results (§3.4; page not provided) report improved HbA1c when berberine was added to metformin, sulfonylureas, or DPP-4 inhibitors. They do not establish an additive effect with a GLP-1 receptor agonist or with any background antidiabetic agent: adding berberine to insulin showed no statistically significant HbA1c benefit. The Discussion (§4; page not provided) also notes exceptions and uncertainty in the subgroup findings. (LLM, conf=0.88)

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Authors
Wang, J., Bi, C., Xi, H., & Wei, F.
Affiliations
Shandong University of Traditional Chinese Medicine (CN)
Corresponding author
Wei, Fengqin
ORCID
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2024-11-21
Volume
15
Pages
1455534-1455534
ISSN
1663-9812 (ISSN-L)
DOI
10.3389/fphar.2024.1455534
PMC
PMC11617981
OpenAlex
W4404597028
Cited by
13
References
65
Citations by year
2026: 3 · 2025: 10
FWCI
0.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
berberine, type 2 diabetes, antidiabetic drugs, combination therapy, fasting blood glucose, postprandial blood glucose, HbA1c, insulin resistance, lipid profile, LDL cholesterol, triglycerides, fasting insulin, HOMA-IR, inflammatory markers, herbal medicine, drug safety, adverse effects, tolerability, cost-effectiveness, quality of life

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